Tinnitus and depression.

OBJECTIVES: Depressive symptoms are common in individuals with tinnitus and may substantially aggravate their distress. The mechanisms, however, by which depression and tinnitus mutually interact are still not fully understood. METHODS: Here we review neurobiological knowledge relevant for the interplay between depression and tinnitus. RESULTS: Neuroimaging studies confirm the existence of neural circuits that are activated both in depression and tinnitus. Studies of neuroendocrine function demonstrate alterations of the HPA-axis in depression and, more recently, in tinnitus. Studies addressing neurotransmission suggest that the dorsal cochlear nucleus that is typically hyperactive in tinnitus, is also involved in the control of attention and emotional responses via projections to the locus coeruleus, the reticular formation and the raphe nuclei. Impaired hippocampal neurogenesis has been documented in animals with tinnitus after noise trauma, as in animal models of depression. Finally, from investigations of human candidate genes, there is some evidence to suggest that variant BDNF may act as a common susceptibility factor in both disorders. CONCLUSIONS: These parallels in the pathophysiology of tinnitus and depression argue against comorbidity by chance and against depression as pure reaction on tinnitus. Instead, they stand for a complex interplay between tinnitus and depression. Implications for tinnitus treatment are discussed.

Chemical speciation and sequential extraction of Mn in workroom aerosols: analytical methodology and results from a field study in Mn alloy plants.

Workers in the Mn alloy producing industry are exposed to aerosols containing a variety of Mn compounds (MnO, MnO,, Mn2O3, Mn3O4, FeMn and SiMn). This paper reports a novel four-step chemical speciation/ fractionation procedure developed for characterisation of workroom aerosols collected in Mn alloy producing plants. The following components of the aerosol have been quantified: "water soluble" Mn dissolved in 0.01 M ammonium acetate: Mn0 and Mn2+ dissolved in 25% acetic acid; Mn3+ and Mn4+ dissolved in 0.5%) hydroxylamine hydrochloride in 25%) acetic acid; and "insoluble" Mn digested in aqua regia and hydrofluoric acid. Dissolution of pure Mn compounds with well-defined stoichiometries were essentially complete in the respective leaching steps with detectable amounts of < 1% in others. Recoveries of a mixed quality control sample were also acceptable in the range 92-97% for the different oxidation states. The levels measured in the inhalable and respirable fractions in three Mn alloy producing plants were approximately 300 and 35 microg m(-3) of total Mn, respectively. The most obvious feature of the speciation results is that none of the work areas is characterised by a single Mn contaminant. The predominant oxidation states in the inhalable aerosol fraction are Mn0 and Mn2+ independent of job functions/departments. The occurrence of insoluble Mn compounds in both the inhalable and respirable aerosol fractions is significantly higher during production of SiMn.

Preliminary report of trace elements in mothers and newborns living in the Kola Peninsula and Arkhangelsk region of Russia compared to Norwegian populations.

Recently, considerable attention has been allotted to the possible health effects of the industrial pollution in the regions adjoining the Norwegian-Russian border. As a measure of general health, the status of trace elements and some clinical-chemical parameters in serum and blood that reflect general health was assessed for 50 consecutive obstetric patients presenting at delivery departments of local hospitals in the Kola Peninsula, Arkhangelsk and selected centres in Norway. A written questionnaire and consent form were completed by each participant. Specimens of maternal and cord blood were collected. Corresponding samples were analyzed for copper, zinc, selenium, iron and ferritin. We found a lower birth weight in the Russian centres. The measurement of trace elements showed a higher iron status for the Russian females and relatively low serum zinc levels were observed in both the Russian and the Norwegian communities. It may be concluded that with the exception of zinc, the mineral status in the Norwegian and Russian arctic centres considered appears to be satisfactory.

Ruminant uptake of nickel and other elements from industrial air pollution in the Norwegian-Russian border area.

Concentrations of the elements aluminium, arsenic, cadmium, chromium, cobalt, copper, lead, mercury, nickel, selenium and zinc in liver, and of nickel in kidneys, were studied in reindeer, moose and sheep from South Varanger in eastern Finnmark and comparable districts in western Finnmark, Norway. The study included samples from 31 reindeer, 10 moose and 10 sheep from Jarfjord (South Varanger); 31 reindeer, 27 moose and 15 sheep from Pasvik (South Varanger); and 40 reindeer, 16 moose and 15 sheep from western Finnmark. Levels of arsenic, copper, nickel and selenium were much higher in reindeer from one or both areas in South Varanger than in reindeer from western Finnmark. Levels of chromium, cobalt and zinc were also significantly higher in South Varanger reindeer than in reindeer from the reference area. Within South Varanger the highest levels of these elements were invariably found in the Jarfjord area. For the other elements studied hepatic levels in South Varanger were similar to or lower than in western Finnmark. Also in moose, higher levels of nickel and of selenium (Jarfjord only) were found in the South Varanger samples than in samples from western Finnmark. In sheep, on the other hand, levels in South Varanger samples were similar to levels in western Finnmark for all the elements studied. Comparing the results with reports on pollution of air and vegetation, it was concluded that for all the elements showing higher levels in reindeer and moose from South Varanger compared to the reference areas, the effect most probably was a result of atmospheric transport of industrial pollution from the nearby Russian towns Nikel and Zapoljarnij. The geographical and interspecies differences within the South Varanger samples support this conclusion.

Beneficial effects of intensive plasma exchange followed by immunosuppressive therapy in severe Graves' ophthalmopathy.

Nine patients with severe Graves' ophthalmopathy were treated by intensive plasma exchange, followed by immunosuppression. Severity of ocular involvement and response to therapy were evaluated by numerical scoring (ophthalmopathy index) and clinically. Serum thyroid stimulating immunoglobulins (TSI) and urinary excretion of glycosaminoglycans (GAG) were measured immediately before and immediately after plasmapheresis. Plasma exchange was rapidly accompanied by marked clinical improvement in 8/9 patients. The most marked effects were on soft tissue involvement, proptosis, intraocular pressure, and visual acuity. The ophthalmopathy index decreased from 9.7 +/- 4.1 to 5.7 +/- 2.2 (p less than 0.001) after plasmapheresis. Serum TSI levels were initially elevated in 6 patients and remained positive in 3 patients after treatment. Urinary GAG excretion was initially 2- to 12-fold normal levels and was decreased by 60%. After plasmapheresis, patients received immunosuppressive drugs for 3-6 months. The follow-up period, after withdrawal of drugs, ranged from 5 to 38 months with a median of 17 months. The ocular condition remained stable in 6 patients. Three patients had a relapse 1 year after plasmapheresis: they were treated a second time by plasma exchange with subsequent improvement. In conclusion, intensive plasma exchange provided prompt and effective improvement in patients with severe progressive Graves' ophthalmopathy. This therapeutic procedure, followed by immunosuppression, gave long lasting results. Relapses were responsive to plasmapheresis therapy. The data suggest that plasma exchange may represent the best primary treatment for severe progressive Graves' ophthalmopathy.

In vitro effects of thyroid hormones on red blood cell Ca++-dependent ATPase activity.

Thyroid hormones (TH) have been shown to exert a direct stimulatory effect on the Ca++-dependent ATPase from human and other mammalian erythrocytes. In this in vitro system, T4 has been shown to be more effective than T3. In the present study, TH effects on Ca++-dependent ATPase were investigated, using rabbit and human erythrocyte membranes, after preincubation with 10(-10) M T4, in the presence or in the absence of exogenous calmodulin (CaM) (5.10(-12) M to 5.10(-9) M). Ca++-dependent ATPase activity was measured as inorganic phosphate (Pi) release from 1 mM ATP. The results showed that basal Ca++-dependent ATPase activity in rabbits was moderately increased by T4 (1.44 +/- 0.05 vs 1.32 +/- 0.04 mumol Pi/mg protein/90 min, mean +/- SE; p less than 0.05). The time course of Pi release did not show any stimulatory effect of T4 during the first hour of incubation. The effect of T4 became apparent, however, 1 h after the addition of ATP (delta T4: 15%). With human membranes, T4 induced a relative stimulation of the Ca++-dependent ATPase of 8-10% (p less than 0.05) in experimental conditions where the enzyme was not maximally stimulated by CaM (delta CaM over basal activity: 5-40%). In conditions of high CaM stimulation (delta CaM: 50-320%), T4 had no effect. These results confirm that Ca++-dependent ATPase activity is increased by T4. The effect of T4 is small, and appears as a late event during incubation with ATP. Stimulation by T4 is expressed in states of low enzyme activation by CaM.(ABSTRACT TRUNCATED AT 250 WORDS)

Beneficial effects of intensive plasma exchange followed by immunosuppressive therapy in severe Graves' ophthalmopathy.

Nine patients with severe Graves' ophthalmopathy were treated by intensive plasma exchange, followed by immunosuppression. Severity of ocular involvement and response to therapy were evaluated clinically by numerical scoring (ophthalmopathy index). Serum thyroid stimulating immunoglobulins (TSI) and urinary excretion of glycosaminoglycans (GAG) were measured immediately before and immediately after plasmapheresis. Plasma exchange was rapidly accompanied by marked clinical improvement in 8/9 patients. The most marked effects were on soft tissue involvement, proptosis, intraocular pressure, and visual acuity. The ophthalmopathy index decreased from 9.7 +/- 4.1 to 5.7 +/- 2.2 (P less than 0.001) after plasmapheresis. Serum TSI levels were initially elevated in 6 patients and remained positive in 3 patients after treatment. Urinary GAG excretion was initially 2- to 12-fold normal levels and was decreased by 60%. After plasmapheresis, patients received immunosuppressive drugs for 3-6 months. The follow-up period, after withdrawal of drugs, ranged from 5 to 38 months with a median of 17 months. The ocular condition remained stable in 6 patients. Three patients had a relapse 1 year after plasmapheresis: they were treated a second time by plasma exchange with subsequent improvement. In conclusion, intensive plasma exchange provided prompt and effective improvement in patients with severe progressive Graves' ophthalmopathy. This therapeutic procedure, followed by immunosuppression, gave long lasting results. Relapses were responsive to plasmapheresis therapy. The data suggest that plasma exchange may represent the best primary treatment for severe progressive Graves' ophthalmopathy.

Absence of circulating desialylated thyroxine-binding globulin in patients with hepatobiliary disease.

Thyroxine-binding globulin (TBG) is the major thyroid hormone carrier protein. The molecule contains approximately 10 sialic acid residues which play a key role in the peripheral metabolism of TBG. Since the serum of patients with liver disease often contains large amounts of several desialylated glycoproteins, the aim of the present studies was to characterize circulating TBG and to examine the possible presence of desialylated TBG (dTBG) in 24 patients with a variety of hepatobiliary diseases and selected on the basis of elevated serum levels of desialylated glycoproteins. Using 4 immunochemical techniques applied for the measurement of TBG, for the detection of dTBG and for the characterization of TBG microheterogeneity, the results indicated: a) a wide scatter of serum TBG levels between 4 and 23 mg/l; b) the absence of detectable amounts of dTBG in any of the sera tested; and c) a close similarity between the microheterogeneity of TBG in patients with liver disease with that of control sera or of purified TBG. In conclusion, in patients with acute and chronic liver disease, TBG, although quantitatively modified, remains qualitatively unaltered, suggesting that diseased liver produces fully sialylated TBG and that its catabolism is not impaired.

Comparison of human thyroxine-binding globulin purification by affinity chromatography procedures.

Three procedures for the isolation of thyroxine-binding globulin from human serum, using affinity chromatography on triiodothyronine (T3) linked to Sepharose (A), thyroxine (T4) linked to Sepharose (B) or T3 linked to epoxy-Sepharose (C) as the first purification step, were compared. With the use of additional purification steps, the three procedures yielded pure thyroxine-binding globulin without desialylation. With procedure A, the initial binding of T4-binding globulin to T3-Sepharose was very low, yielding a poor final recovery (17%). Procedure B gave the highest yield (35%) after a three-step purification, with a low T4 content (0.15-0.30 mol/mol). Procedure C also gave a high yield (28%) after only two purification steps, with a T4 content greater than 0.7 mol/mol. The microheterogeneity of T4-binding globulin obtained with these three procedures was demonstrated by isoelectric focusing: five major bands were observed between pH 4.1 and 4.6, and intermediate faint bands (often doublets) in the same pH range. However, with procedures A and C, the most acidic bands (pH 4.10-4.20) were always absent. Thyroxine-binding globulin was preincubated with radioactively labelled T3 or T4 and the hormone-protein complex was analyzed by isoelectric focusing. The binding of T3--compared to that of T4--was reduced in the most acidic protein subspecies. These results suggest differences in the thyroid hormone binding properties of the various subspecies of human T4-binding globulin.

[Use of plasmapheresis in a case of Graves' disease with malignant ophthalmopathy (author's transl)]. / Exophtalmie maligne traitée par échange plasmatique. Rapport d'un cas.

A short trial with high doses of prednisolone to treat a 62 year-old woman with malignant ophthalmopathy due to Graves disease yielded an unsatisfactory improvement after 5-6 days. The authors decided therefore to use plasmapheresis, 4 plasma exchanges of 2.5 liters each associated with prednisolone (80 ng/day) and azathioprine (100 mg/day). This therapeutic approach resulted in a spectacular improvement obtained after less than 2 weeks: normalization of thyroid function, improvement of all ophthalmological indices confirmed by radiology (C.A.T.) of the retroocular region. The rapid and important improvement obtained after such a short period of time is in favor or the major role of plasmapheresis in this combined therapy of malignant Graves' ophthalmopathy.

Characterization of protein phosphokinase activities in horse thyroid nuclei.

The distribution of protein phosphokinase (EC 2.7.1.37) activities has been established in horse thyroid nuclei. The presence of several enzyme activities has been demonstrated, two of which are clearly distinct. The first one acts on histone as substrate and is activated by cyclic AMP. Physico-chemical properties of this nuclear cyclic AMP-dependent histone kinase and of the cytosol histone kinase are different, demonstrating the absence of a contamination from the cytosol. The second enzyme acts on casein as substrate and is not stimulated by cyclic AMP POR CYCLIC GMP. The findings are consistent with the observation of thyrotropin stimulation of histone phosphorylation in thyroid nuclei.