D2 dopaminergic and 5-HT1A serotonergic activity of 2-(1-naphthyl)ethyl- and 2-(2-naphthyl)ethyl amines.

Several tertiary 2-phenylethyl, 2-(1-naphthyl)ethyl and 2-(2-naphthyl)ethyl amines were synthesized and their binding affinities for dopamine D(1), D(2) and serotonin 5-HT(1A) receptors evaluated in radioligand binding assays. All compounds were inactive in D(1) dopamine radioligand binding assay. The 2-(1-naphthyl)ethyl analogues expressed a low but significant binding affinity for the D(2) and moderate one for the 5-HT(1A) receptor subtypes. Most of the remaining compounds expressed binding affinity at the 5-HT(1A) receptor subtype but were inactive in D(2) receptor binding assay. Based on these results and considering the chemical characteristics of the compounds synthesized and evaluated for dopaminergic and serotonergic activity throughout the present study it can be concluded that hydrophobic type of interaction (stacking or edge-to-face) plays a significant role in the formation of receptor-ligand complexes of 2-(1-naphthyl)ethyl amines. This structural motive can be applied to design and synthesize new, more potent dopaminergic/serotonergic ligands by slight chemical modifications.

Investigation of mixed D2/5-HT1A activity of N-heteroarylmethyl-N-phenylpiperazines, N-heteroarylethyl-N-phenylpiperazines and N-heteroarylpropyl-N-phenylpiperazines.

Eight novel N-heteroarylalkyl-N-phenylpiperazines have been synthesized, chemically characterized and evaluated for in vitro binding affinity at the dopamine and serotonin receptors. Synaptosomal membranes of fresh bovine caudate nuclei (D1 and D2), the membranes of COS-7 cells (D4.4) and those prepared from fresh bovine hippocampi (5-HT1A) were used as a source of the corresponding receptor subtypes. [3H]SCH 23390 (D1-selective), [3H]spiperone (D2- and D4.4-selective) and [3H]-8-OH-DPAT (5-HT1A-selective) served as radioligands. None of the compounds expressed the affinity for the binding at the D1 subtype receptor. Compounds 7-9 containing a single methylene group serving as a bridge between heteroaryl- and N-phenylpiperazine part of the molecule were inactive [3H]spiperone and [3H]-8-OH-DPAT competitors. Ligands 15-19 (three methylene groups connecting heteroaryl- and N-phenylpiperazine part of the molecule) acted as moderate competitors of [3H]spiperone binding at the D2 receptor subtype, with the exception of 15 (a thione) which expressed a high binding affinity at the D2 receptor subtype. Compounds 15-19 behaved as moderate displacers of 8-OH-[3H]DPAT. Among all eight novel ligands only compound 15 expressed a moderate binding affinity at the D4.4 receptor subtype.

Hyperbaric oxygen as a method of therapy of sudden sensorineural hearing loss.

Sudden hearing loss is a sensorineural hearing impairment, which develops over a period of few hours to a few days. Several theories have been proposed regarding the development of sudden sensorineural hearing loss. The incidence of sudden sensorineural hearing loss has been reported to range from 5 to 20 per 100,000 persons per year. Hearing loss is treated with drugs that provide better blood supply to the inner ear and decrease inflammation. The aim of this study is to examine the influence of hyperbaric oxygen therapy in treating sudden sensorineural hearing loss. The beneficial effects of HBO2 on sudden sensorineural hearing loss are probably achieved by an increase in the distribution of O2 dissolved per volume unit of blood circulating trough the regions affected by the lack of oxygen. Sessions were performed on 17 patients, with sudden sensorineural hearing loss that began within 10 days prior to the tests. In the hyperbaric chamber, all patients breathed 100% oxygen at 2.8 bars, for 60 minutes twice a day, either until recovered or for a maximum of 30 sessions. Of the total number of study participants, 12 were male and 5 were female, and their average age was 35.3 years (range: 18 to 68). Before the therapy, an average hearing value was obtained out of five basic frequencies. Hearing was found to be in the range of 61-93 dB in 12 patients, while 5 patients had hearing in the range of 41-60 dB. Following therapy with hyperbaric oxygen, the hearing level of 14 patients was within the range of 0-26 dB, two patients' hearing level increased to 27-40 dB, and one patient's hearing level remained in the range of 41-60 dB. The average hearing level for all patients and for all five basic frequencies was 67.8 dB before therapy, in comparison with 21.6 dB after oxygen therapy (p=0.0003). The average number of sessions in the hyperbaric chamber was 11.9 (range: 5 to 20). The therapy was taken well by all patients. The results of this study, as well as the results of similar studies performed by other authors, indicate for the necessity of performing an additional prospective, random, double-blind study of the effects of hyperbaric oxygen therapy on sudden sensorineural hearing loss, on a large number of patients.

Introduction of a methyl group in alpha- or beta-position of 1-heteroarylethyl-4-phenylpiperazines affects their dopaminergic/serotonergic properties.

1-(2-Heteroarylalkyl)-4-phenylpiperazines containing methyl group in either the alpha- or the beta-position of the side alkyl chain were synthesized as racemic mixtures. They were evaluated for in vitro binding affinity at the D1 and D2 dopamine and 5-HT1A serotonin receptors using synaptosomal membranes of the bovine caudate nucleus and hippocampus, respectively, as a source of the corresponding receptors. Tritiated SCH 23390 (D1 receptor-selective), spiperone (D2 receptor-selective), and 8-OH-DPAT (5-HT1A receptor-selective) were employed as the radioligands. None of the new compounds expressed significant affinity for the D1 receptor. Introduction of the methyl group into the beta-position of the parent molecules increased the affinity for the D2 receptor (10b-13b), and decreased the affinity for the 5-HT1A receptor with the exception of imidazole (11b) which was a rather efficient displacer of 8-OH-DPAT. Most potent of the newly synthesized compounds in [3H]spiperone assay were compounds (+/-)6-[1-methyl-2- (4-phenylpiperazin-1-yl)-ethyl]-1,4-dihydroquinoxaline-2,3-dione (10b), Kd = 6.0 nM and (+/-)5-[1-methyl-2-(4-phenylpiperazin-1-yl)-ethyl]-1,3-dihydrobenzoimidazol- 2-thione (13b), Kd = 5.3 nM. However, compounds containing methyl group in alpha-position (10a-13a) of the parent molecules expressed a decreased affinity for the D2 receptor, while the affinity for the 5-HT1A receptor remained in the same range of concentrations as that of closely related achiral parent compounds (14-17) run in the same binding assays as references.

Hyperbaric oxygen for the treatment of nonarteritic anterior ischemic optic neuropathy.

This clinical study tackled the problem of hyperbaric oxygen in patients with nonarteritic anterior ischemic optic neuropathy. Twenty-one patients were included in the study. The patients were divided into two groups: experimental and control. Experimental group consisted of 10 patients, who had been previously treated with corticosteroids, without significant success. In four patients with a clinical picture of PNO atrophy, medical steroid treatment failed to any significant improvement in visual acuity. In 6 patients, however, this treatment resulted in a significant improvement of both visual acuity and field of vision. These patients showed further improvement on control testing performed six month later. All patients from the control group were treated with corticosteroids per os and by local application, but without any significant improvement as revealed by visual acuity and visual field testing. Authors' results pointed the possibility of conservative treatment of patients with anterior ischemic optic neuropathy, especially those in whom steroid therapy had proved inefficient.

The effects of hyperbaric oxygen on visual functions in ischaemic optic neuropathy.

The effects of hyperbaric oxygen therapy were studied in nine patients with non-arteritic anterior ischaemic optic neuropathy, who had been unsatisfactorily treated with corticosteroids. In four patients with signs of optic disc atrophy there was no improvement of visual functions after hyperbaric oxygen treatment, whereas in the other five patients, who had no signs of optic disc atrophy, visual acuity and visual field improved. The achieved improvements were maintained at a control examination six months later. Results suggest that hyperbaric oxygen might be a new remedy for the selected cases of non-arteritic ischaemic optic neuropathy and call for a controlled clinical study aiming to accurately assess its efficacy.

Military injuries to the popliteal vessels in Croatia.

OBJECTIVE: The paper reviews military popliteal vascular injuries in Croatia. SUMMARY BACKGROUND DATA: Popliteal vascular injuries still pose difficult problems for vascular surgeons despite improvements in resuscitation, surgical techniques and wound coverage. Popliteal vascular injuries, both arterial and venous, with a high incidence of associated musculoskeletal injuries are presented in patients with military injuries in South Croatia. METHODS: 26 wounded with popliteal vascular injuries are presented. Explosive injuries are found in 21 and associated fractures in 9 cases. In immediate repair group the time interval between trauma and surgery was 2 to 30 hours (average 9.8 hours). In the delayed repair group the interval between trauma and surgery was 11 days to 24 days. RESULTS: 21 out of 26 patients with popliteal vascular injuries had combined arterial and venous injuries; 4 patients had isolated popliteal arterial injuries, while 8 patients had other vascular injuries along with the popliteal ones; 8 amputations resulted (30.8%). CONCLUSION: Popliteal vascular injuries caused by typical military mechanism during the war in Croatia present large and extensive defects of tissues and bones, are often associated with other injuries and require more extensive surgical therapy. Evacuation of the wounded under very difficult conditions as well as considerable organization and transportation problems are characteristic for this war and greatly affect the success of vascular reconstruction. Hyperbaric oxygen therapy offers a safe noninvasive method of improving wound healing and decreasing edema formation in popliteal vascular injuries.

Hyperbaric oxygen dose of choice in the treatment of glaucoma.

The subjects in the study were 111 patients with open angle glaucoma who were submitted to treatment by hyperbaric oxygenation. Two groups were formed at random, an experimental one of 91 patients and a control group of 20 patients. The experimental group consisted of four subgroups classified according to the course of treatment they received: 30 sessions (31 patients), 20 sessions (20 patients), 15 sessions (20 patients) and 10 sessions (20 patients). For the treatment a large walk-in recompression chamber was utilized, once a day, at a pressure of 2.0 bars, for 90 minutes. Visual acuity and mean intraocular pressure values taken before and after hyperbaric oxygen treatment did not show a statistically significant difference either between the treated and control subjects, or at control examinations after three and six months. During the follow-up period, changes in the visual field area in control subjects were discrete and statistically not significant. At the same time the visual field values increased after the therapy in all the subgroups. In the 10-session course subgroup the increase was not statistically significant. In all other subgroups, statistical significance was at the level of P < 0.01. Control after three months demonstrated the same level of statistical significance; control at the end of six months failed to show a statistically significant difference. The 20-session course is recommended for initial treatment. When visual field values return to 50 percent of the improved values achieved during initial treatment, it is suggested that hyperbaric oxygen treatment be repeated.