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.     

Endothelin-1 in children with chronic renal failure

Endothelin-1 (ET-1) was meansured after extraction from plasma of normal adults (5.9±1.9 pg/ml,n=22), normal children (7.1±1.86 pg/ml,n=29), nonhaemodialysed children with chronic renal failure (CRF) (11.1±1.8 pg/ml),n=10), renal graft recipients (9.5±3.4 pg/ml,n=37), haemodialysed children 24 h after a haemodialysis session (20.02±10.9 pg/ml,n=26) and haemodialysed children before and after a haemodialysis session (15.31±10.6 and 13.8±8.5 respectively,n=14). A sensitive and specific radioimmunoassay was used. ET-1 was significantly higher in non-haemodialysed CRF children and in renal graft recipients than in normal children (P<0.001 andP<0.01, respectively) and significantly higher in haemodialysed children when compared with normal children, non-haemodialysed CRF children and renal graft recipients (P<0.001). ET-1 concentrations were similar in normal children and normal adults. ET-1 was inversely correlated with glomerular filtration rate in non-haemodialysed CRF children (r=–0.39,P<0.01) and positively correlated with extracellular volume in haemodialysed children (r=0.435,P<0.03). After haemodialysis, ET-1 increased in 6 and decreased in 8 of the 14 children studied before and after a haemodialysis session.     

Effectiveness of gentamicin-impregnated cement in the prevention of deep wound infection after primary total knee arthroplasty.

Effectiveness of gentamicin-impregnated cement in preventing deep wound infection after total knee arthroplasty (TKA) was estimated using data from prospective surveillance. In multivariate analysis, the protective effect of gentamicin-impregnated cement on the development of infection was close to the limit of significance. Gentamicin-impregnated cement may prevent TKA infections.     

Brain protection at the blood-cerebrospinal fluid interface involves a glutathione-dependent metabolic barrier mechanism.

The choroid plexuses (CPs) form a protective interface between the blood and the ventricular cerebrospinal fluid (CSF). To probe into the pathways by which CPs provide brain protection, we sought to evaluate the efficiency of glutathione conjugation in this barrier as a mechanism to prevent the entry of blood-borne electrophilic, potentially toxic compounds into the CSF, and we investigated the fate of the resulting metabolites. Rat CPs, as well as human CPs from both fetal and adult brains, displayed high glutathione-S-transferase activities. Using an in vitro model of the blood-CSF barrier consisting of choroidal epithelial cells cultured in a two-chambered device, we showed that glutathione conjugation can efficiently prevent the entry of 1-chloro-2,4-dinitrobenzene (CDNB) into the CSF, a model for electrophilic compounds. The duration of this enzymatic protection was set by the concentration of CDNB to which the epithelium was exposed, and this barrier effect was impaired only on severe epithelial intracellular glutathione and cysteine depletion. The conjugate was excreted from the choroidal cells in a polarized manner, mostly at the blood-facing membrane, via a high-capacity transport process, which is not a rate-limiting step in this detoxification pathway, and which may involve transporters of the ATP-binding cassette c(Abcc) and/or solute carrier 21 (Slc21) families. Supplying the choroidal epithelium at the blood-facing membrane with a therapeutically relevant concentration of N-acetylcysteine sustained this neuroprotective effect. Thus, glutathione conjugation at the CP epithelium coupled with the basolateral efflux of the resulting metabolites form an efficient blood-CSF enzymatic barrier, which can be enhanced by pharmacologically increasing glutathione synthesis within the epithelial cells.     

Course of depressive symptoms and medication adherence after acute coronary syndromes: an electronic medication monitoring study.

OBJECTIVES: We tested whether improvements in depressive symptoms precede improved adherence to aspirin in patients with acute coronary syndromes (ACS). BACKGROUND: Depression is associated with medication nonadherence in patients with ACS, but it is unclear whether changes in depression impact on adherence. METHODS: Electronic medication monitoring was used to measure adherence to aspirin during a 3-month period in a consecutive cohort of 172 patients (25 to 85 years) recruited within 1 week of hospitalization for ACS. Depressive symptom severity was assessed using the Beck Depression Inventory (BDI) during hospitalization and at 1 and 3 months after hospitalization. Adherence was defined as the percentage of days aspirin was taken as prescribed. RESULTS: Depression severity in hospital was associated with nonadherence in a gradient fashion: 15% of non-depressed patients (BDI score 0 to 4), 29% of mildly depressed patients (BDI score 10 to 16), and 37% of patients with moderately-to-severely depressive symptoms (BDI score >16) took aspirin less than 80% of the time (p = 0.03). A cross-lagged path analytic model revealed that improvements in depressive symptoms in the first month after the ACS were associated with improvements in adherence rates in the subsequent 2 months (standardized direct effect -0.32, p = 0.016). CONCLUSIONS: Diagnosis and treatment of depressive symptoms may improve medication adherence in patients after ACS.     

Association of donor TNFRSF6 (FAS) gene polymorphism with acute rejection in renal transplant patients: a case-control study.

BACKGROUND: Genetic factors other than HLA have been reported to be associated with the outcome of organ transplantations. Because binding of FasL to its receptor Fas could play an important role in tubulitis and in the death of graft tubular epithelial cells during kidney allograft rejection, a gene polymorphism recently identified in position -671 in the promoter of the TNFRSF6 gene coding for Fas was investigated in donors. METHODS: A case-control study was performed within a cohort of non-hyperimmunized adult patients who had received cadaveric kidney transplants based on the occurrence or absence of acute cellular rejection in the first 6 months after renal transplantation. Each recipient from the acute rejection group (n = 35) was matched for age (+/- 5 years) and number of HLA-DR mismatches with two recipients within the non-acute rejection group (n = 70). RESULTS: The TNFRSF6-GG genotype was more frequent in donors in the group without rejection episodes. In contrast, patients who received a kidney from a TNFRSF6-A carrier were more likely to experience acute rejection episodes (relative risk nearly 2.1). CONCLUSION: This study suggests that donor TNFRSF6 polymorphism directly or indirectly influences acute kidney rejection episodes.     

Delay of cranial bone regeneration by CO2 and Nd-YAG laser application: an experimental study related to craniosynostosis

In this study we have investigated the negative influence of CO₂ and Nd-YAG laser irradiation on rapid cranial regeneration and whether it has any use in certain types of craniosynostosis. Twenty-two newborn rats were used in the study. Both CO₂ and Nd-YAG laser irradiation, which was applied to free bony edges after, suturectomies, resulted in a significant decrease in skull regeneration. Histopathological examinations revealed severe degeneration caused by both types of laser energies.     

Use of the free prefabricated temporoparietal fascia-chondro-cutaneous flap nourished by only arterial inflow: an arterial flap

Summary Pedicled temporoparietal fascial flaps have been used extensively in head and neck reconstruction for many years. Also, the fascia has been grafted, and the skin graft transformed into a vascularized pedicled flap (prefabricated temporoparietal fasciocutaneous flap). On the other hand, some authors have used free temporoparietal fascial flaps for defects that require to be filled in lower and upper extremity wounds. In this case, a free prefabricated temporoparietal fascio-chondro-cutaneous flap having only an arterial inflow was used in eyelid reconstruction.Presented at the 14th Congress of Turkish Plastic and Reconstructive Surgery, Ankara, Turkey, October 1992     

Thymidylate synthase activity,folates, and glutathione system in head and neck carcinoma and adjacent tissues

Background. Head and neck squamous cell carcinomas (HNSCC) present variable aggressiveness and chemosensitivity. Because the glutathione (GSH) system and thymidylate synthase (TS) are involved in the resistance to the main drugs used in HNSCC (cisplatin and 5-FU), we studied these systems in tumors and normal mucosae. Methods. Tumor samples and normal adjacent mucosae were collected from 37 untreated HNSCC patients. GSH and glutathione S-transferase (GST) activity were assayed by spectrophotometry, whereas TS activity and folates were determined by radioassays. Results. Mean GSH levels were higher in tumors (15.2 ± 8.2 nmol/mg protein) than in mucosae (8.3 ± 4.1 nmol/mg protein) (p = 0.005, paired t test). GST activity was also higher in tumors (394 ± 194 nmol/min/mg protein) than in mucosae (261 ± 132 nmol/min/mg protein) (p = 0.0003). TS activity was markedly higher in tumors (9.2 ± 21.5 pmol/min/mg protein) compared to that of mucosae (0.9 ± 1.2 pmol/min/mg protein) (p = 0.0001). Folate levels in tumors and mucosae were similar (1.2 ± 1.1 and 0.8 ± 0.9 pmol/mg protein, respectively; p = 0.1, NS). In relation to clinical stage and tumor size, a statistical difference was found in GSH and GST values between tumors and mucosae for stage IV and T3/T4. The increase in tumor TS compared to that of mucosae was significant for all clinical stages, tumor sizes, and nodal involvement. Conclusions. These data enhance our understanding of the enzymatic systems involved in cisplatin and 5-fluorouracil (5-FU) resistance in HNSCC and normal mucosae and may help to elucidate tumor behavior and interpatient differences in drug sensitivity. © 1994 John Wiley & Sons, Inc.