Comparison between short- and long-term haloperidol administration on somatostatin and substance P concentrations in the rat brain

Neuroleptics influence a variety of putative neurotransmitters in the basal ganglia, including somatostatin and substance P. Most studies have been performed in animals after only 3 or 4 weeks of neuroleptic administration and have seldom examined the effects of withdrawal. To understand better the effects of haloperidol on neuropeptide systems, the effects of short-term (3 weeks) and long-term (8 months) administration, as well as withdrawal from long-term administration of haloperidol, on somatostatin and substance P concentrations were examined in the rat. Short-term haloperidol significantly decreased the concentrations of somatostatin in the caudate-putamen, nucleus accumbens, and ventral tegmental area, and decreased the concentration of substance P in the substantia nigra and the nucleus accumbens. However, long-term administration only decreased the concentration of somatostatin in the nucleus accumbens. In addition, a slight reduction in the concentration of substance P in the medial prefrontal cortex was detected after long-term treatment. After withdrawal from long-term haloperidol administration the concentrations of these peptides did not differ from control values in any of the brain regions examined. These results confirm that dopamine receptor blockade can affect the somatostatin and substance P systems in the basal ganglia and indicate that during long-term administration (8 months) tolerance develops to some of the effects that are observed after shorter (3 weeks) treatment periods.     

Growth hormone releasing activity by intranasal administration of a synthetic hexapeptide (hexarelin)

OBJECTIVE Hexarelin is a new synthetic growth hormone releasing peptide. We have tested the efficacy of intranasal (i.n.) administration of hexarelin to stimulate plasma GH and have compared this to the intravenous (i.v.) administration of the peptide. PATIENTS Ten children with familial short stature (FSS) aged 5·5-15·5 years and two known GH deficient patients aged 24 and 28 years without GH treatment. METHODS All 12 subjects were submitted to i.v. (1 μg/kg) and i.n. (20 μg/kg) hexarelin tests with a one-week interval between tests. Blood samples for GH, TSH, fT4 and T3 were obtained at 0, 15, 30, 60, 90 and 120 minutes. The hormone determinations were made by standard radio-immunoassays (RIA). RESULTS Both the i.n. and i.v. administration of hexarelin induced a large GH response, the mean (±SD) being 72·2± 35·5 mU/l for the i.n. test and 79·6 ± 53·0 mU/l for the i.v. test. The peak GH in the i.v. test occurred at 15–30 minutes and in the i.n. test between 30 and 60 minutes. The GH deficient patients showed no GH response In either test. Plasma TSH decreased in the FSS children from a mean (±SD) of 1.0 ± 0·26 to 0·64±0 2 mU/l (P<0 005) during the i.n. test and from 1·0±0·3 to 0·7±0·3mU/l (P> 0 05) during the I.v. test. In the isolated GH deficient patient, plasma TSH decreased from 1·06±0·38 mU/l to 0·86±0·17 during the i.v. test and from 1·60±0·01 to 1·11±0·06mU/l during the i.n. test. There were no significant changes in plasma fT4 or T3 in any of the tests. CONCLUSIONS The synthetic hexapeptide hexarelin is a potent pituitary GH stimulator when administered intra-nasally. The GH response was similar to that observed after intravenous hexarelin. Simultaneously, there was a significant decrease in plasma TSH but the concentrations remained in the normal range. These findings appear to be of theoretical and practical relevance to the investigation and management of short children.     

Loss of endogenous androgen receptor protein accelerates motor neuron degeneration and accentuates androgen insensitivity in a mouse model of X-linked spinal and bulbar muscular atrophy

Human Molecular     

Trans-perineal implantation of radio-opaque treatment verification markers into the prostate: an assessment of procedure related morbidity, patient acceptability and accuracy.

On-line imaging of prostate markers can be used to compensate for errors in radiation delivery. This study assessed the patient acceptability and morbidity associated with the trans-perineal route of implantation. A minority experienced acute pain or bleeding. Placement was accurate in all but one subject. An operator related learning curve exists. Although this is an invasive procedure most patients found it acceptable. Implementation for routine clinical practice is feasible.     

Postnephrectomy arteriovenous fistula of the renal pedicle treated with detachable balloons: A case report

A case of postnephrectomy arteriovenous fistula of the right renal pedicle is reported here. The diagnosis was confirmed by angiography, and successful treatment was achieved using detachable balloon.     

Interaction of epidermal growth factor, Ca2+, and matrix metalloproteinase-9 in primary keratinocyte migration

Elevations of epidermal growth factor (EGF) and Ca²⁺ concentrations in the wound site are associated with reepithelialization during wound healing. In addition, Ca²⁺ and EGF can both induce increases in matrix metalloproteinase‐9 (MMP‐9) synthesis. However, little is known about the interplay of these events in regulating the migration properties of primary keratinocytes on collagen I, the most abundant extracellular matrix component in the skin. We found that EGF stimulated both chemokinetic and chemotactic migration of primary keratinocytes on collagen I; however, MMP‐9 was required for EGF‐stimulated chemotaxis but not EGF‐stimulated chemokinesis. Calcium at 0.5 mM stimulated chemokinetic migration of keratinocytes. Together, Ca²⁺ and EGF stimulated higher levels of chemokinesis than either stimulus alone. Furthermore, Ca²⁺ could restore the ability of keratinocytes from MMP‐9 null mice to undergo EGF‐stimulated chemotaxis. The phosphatidylinositol‐3 kinase inhibitor LY294002 inhibited both EGF‐ and Ca²⁺‐stimulated chemokinetic migration. In contrast, the MEK inhibitor PD98059 blocked Ca²⁺‐ but not EGF‐stimulated chemokinetic migration of keratinocytes. A combination of PD98059 and LY294002 was required to inhibit Ca²⁺ enhancement of EGF‐stimulated migration completely. Calcium‐stimulated chemokinesis was completely blocked by either the protein kinase C‐α inhibitor Gö6976 or the src/fyn inhibitor PP2. Using primary keratinocytes, our results showed how the combined action of Ca²⁺, EGF, and MMP‐9 regulated the contributions of extracellular‐regulated kinase and phosphatidylinositol‐3 kinase toward chemokinetic and chemotactic migration of keratinocytes.