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Beta-adrenergic-mediated cyclic AMP accumulation was reduced in lymphocytes obtained from depressed patients from that observed in an age- and sex-matched group of control subjects. Among the depressed patients, those not responding to treatment showed significantly lower pretreatment responses to isoproterenol compared with patients who exhibited significant clinical improvement during antidepressant treatment. Late-night (terminal) insomnia was significantly associated with the blunted response to beta-adrenergic stimulation. In depressed patients with the lowest isoproterenol response, the effect of forskolin (which acts distal to the receptor and directly stimulates the catalytic subunit) on cyclic AMP accumulation was also significantly decreased. This suggests that post-receptor modulations of signal amplification also play a role in the reduced response to beta-adrenergic stimulation in depression. [ABSTRACT FROM AUTHOR]

Light-sheet fluorescence microscopy (LSFM) is a powerful technique that can provide high-resolution images of biological samples. Therefore, this technique offers significant improvement for three-dimensional (3D) imaging of living cells. However, producing high-resolution 3D images of a single cell or biological tissues, normally requires high acquisition rate of focal planes, which means a large amount of sample sections. Consequently, it consumes a vast amount of processing time and memory, especially when studying real-time processes inside living cells. We describe an approach to minimize data acquisition by interpolation between planes using a phase retrieval algorithm. We demonstrate this approach on LSFM data sets and show reconstruction of intermediate sections of the sparse samples. Since this method diminishes the required amount of acquisition focal planes, it also reduces acquisition time of samples as well. Our suggested method has proven to reconstruct unacquired intermediate planes from diluted data sets up to 10× fold. The reconstructed planes were found correlated to the original preacquired samples (control group) with correlation coefficient of up to 90%. Given the findings, this procedure appears to be a powerful method for inquiring and analyzing biological samples., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Growth factors play an important role in nerve regeneration and repair. An attractive drug delivery strategy, termed "magnetic targeting", aims to enhance therapeutic efficiency by directing magnetic drug carriers specifically to selected cell populations that are suitable for the nervous tissues. Here, we covalently conjugated nerve growth factor to iron oxide nanoparticles (NGF-MNPs) and used controlled magnetic fields to deliver the NGF⁻MNP complexes to target sites. In order to actuate the magnetic fields a modular magnetic device was designed and fabricated. PC12 cells that were plated homogenously in culture were differentiated selectively only in targeted sites out of the entire dish, restricted to areas above the magnetic "hot spots". To examine the ability to guide the NGF-MNPs towards specific targets in vivo, we examined two model systems. First, we injected and directed magnetic carriers within the sciatic nerve. Second, we injected the MNPs intravenously and showed a significant accumulation of MNPs in mouse retina while using an external magnet that was placed next to one of the eyes. We propose a novel approach to deliver drugs selectively to injured sites, thus, to promote an effective repair with minimal systemic side effects, overcoming current challenges in regenerative therapeutics.

Tinnitus is poorly reflected by audiometric (cochlear) data, indicating that central nervous system (CNS) components are involved in its development. This study aimed to provide support for the neurophysiological theory of tinnitus as a result of combined peripheral and central nervous dysfunctions. Our main findings were the sudden. significant, stepwise increase in tinnitus after 10 years of service, as opposed to the almost linear increase in noise-induced hearing loss (NIHL) with age. Furthermore, the absence of a correlation between the incidence of tinnitus and the severity of tinnitus was linked to the NIHL. We suggest that, in tinnitus, the central screening apparatus which normally inhibits conscious awareness of irrelevant, spurious and non-informative internal and external noise shows a possibly fatigue- or age-related deterioration over time. Further support was provided by low blood levels of vitamin B1 and B12. which are essential to CNS function.

The role of the auditory brainstem in tinnitus is questionable. This study aimed comprehensively to assess auditory brainstem responses (ABRs) in patients suffering from noise-induced tinnitus (NIT). ABRs were recorded from 13 chronic NIT patients (21 ears) and 11 (21 ears) age and hearing matched control subjects without tinnitus. ABRs were recorded with scalp electrodes placed ipsilateral and contralateral to the stimulated ear, and in three orthonormal differential configurations. The ABRs were analyzed as a function of time, frequency and voltage space. A significantly enhanced ipsilaterally recorded, time domain wave III amplitude was observed for the tinnitus patients. This finding was not confirmed by any of the other ABR measures, which were indistinguishable between subject groups. Although this may be a spurious result, it nonetheless may point to an alteration in the functioning of the putative wave III auditory brainstem generator, which deserves further study.

The psychological profile of tinnitus patients who sought treatment (Help-Seeking, HS) was compared with that of patients who did not seek help (non-help-seeking, NHS) and with normal control subjects. Psychological evaluations as well as hearing, tinnitus loudness, and tinnitus pitch were measured. Overall, the psychiatric symptomatology of HS (n = 50) was more severe with poorer effective coping abilities and externalization of locus of control than NHS (n - 50). However, the psychiatric symptomatology of the NHS was remarkably more severe than that in the normals (n = 73) and more like that in the HS even though they did not turn to treatment. Tinnitus loudness was significantly lower in HS than in NHS subjects. The lower the tinnitus loudness, the higher the psychiatric symptomatology. The trend towards subclinical abnormalities in NHS indicates their vulnerability to pathology and this requires the attention of the therapist in order to increase the patient's self-awareness and to suggest preventive coping strategies or relaxation techniques.

The efficacy of self-hypnosis (SH), masking (MA) and attentiveness to the patient's complaints (AT) in the alleviation of tinnitus was evaluated. Forty-five male patients close in age with chronic tinnitus related to acoustic trauma were assigned to three matched subgroups: SH, AT or MA. The therapeutic stimuli in the SH and MA sessions, recorded on audio cassettes, were given to the patients for use when needed. SH significantly reduced the tinnitus severity; AT partially relieved the tinnitus; MA did not have any significant effect.

Introduction: This study examines the incidence of vitamin B12 deficiency in three groups of noise-exposed subjects: patients with chronic tinnitus and noise-induced hearing loss (NIHL), patients with NIHL only, and subjects demonstrating normal hearing., Materials and Methods: A group of 113 army personnel exposed to military noise was studied. The mean age was 39 years. Chronic tinnitus and NIHL existed in 57 subjects. NIHL alone was observed in 29 subjects, and 27 subjects had normal audiograms. All subjects were queried about noise exposure and dietary habits. Vitamin B12 serum levels were measured., Results: Patients with tinnitus and NIHL exhibited vitamin B12 deficiency in 47% of cases (blood levels < or = 250 pg/mL). This was significantly more (P < .023) compared with NIHL and normal subjects who exhibited vitamin B12 deficiency in 27% and 19%, respectively., Conclusion: These observations suggest a relationship between vitamin B12 deficiency and dysfunction of the auditory pathway. Some improvement in tinnitus and associated complaints were observed in 12 patients following vitamin B12 replacement therapy. The authors recommend that routine vitamin B12 serum levels be determined when evaluating patients for chronic tinnitus.

The efficacy of self-hypnosis (SH) on tinnitus relief was compared with two control procedures: 1) presentation of a brief auditory stimulus (BAS) to the ear with tinnitus; 2) waiting list (WL), i.e. patients receiving no formal treatment. The results have shown that 73% of SH subjects reported disappearance of tinnitus during treatment sessions, as compared with only 24% in the BAS group. Moreover, the short-term (1 week) and long-term (2 months) symptom profiles of only SH subjects revealed a significant improvement. Thus, SH may well be a beneficial method for the relief of tinnitus.

The activity of phosphatidylinositol-specific phospholipase C was significantly reduced in platelets obtained from 20 euthymic manic-depressive patients on therapeutic lithium doses (mean blood level 0.85 mEq/l) compared to an age- and sex-matched group of 36 control subjects. The activities of prostaglandin E1-, aluminum/NaF-, and forskolin-stimulated platelet adenylate cyclase activity were also measured in a similar group of 16 lithium-treated and 22 control subjects. A marked reduction in both postreceptor (aluminum/NaF and forskolin) and receptor-stimulated (prostaglandin E1) platelet adenylate cyclase activity was observed in the lithium-treated group (mean blood level 0.81 mEq/l). These findings support the hypothesis that lithium's therapeutic mode of action in manic-depressive psychosis is mediated by the combined down-regulation of both principal second messenger systems, inositol phosphates and cyclic adenosine monophosphate, by reducing the activity of phosphatidylinositol-specific phospholipase C and adenylate cyclase.

Cyclic adenosine 3',5'-monophosphate (cAMP) signal transduction was examined in lymphocytes and platelets obtained from patients with posttraumatic stress disorder. Intact lymphocytes from the posttraumatic patients (N = 10) showed significantly lower basal, isoproterenol-, and forskolin-stimulated cAMP levels than those from 10 healthy control subjects. In platelet membrane preparations, basal, forskolin-, aluminum chloride plus sodium fluoride-, and prostaglandin E1-stimulated adenylate cyclase activity levels were all significantly lower in the posttraumatic group than in the control group. The authors discuss the potential role of their findings as a biological marker for posttraumatic stress disorder.

Isoproterenol, prostaglandin E1 and forskolin-stimulated cyclic AMP accumulation were compared in intact lymphocytes obtained from nine monozygotic and nine sib pairs matched for age and sex. Heritability was calculated by three different methods, two based on the intraclass correlation coefficients and one based directly on the variances. Only for forskolin is a significant proportion of variance (0.68-0.91) attributable to genetic factors, suggesting that forskolin-stimulated activity may prove to be a valuable genetic marker in studies of human pathology. Neither basal nor isoproterenol and prostaglandin E1-stimulated activity show significant heritability in intact human lymphocytes. The individual differences observed in levels of beta-adrenergic and prostaglandin stimulated receptor activity in human lymphocytes are, therefore, most likely due to environmental factors.

Twenty-two acutely psychotic patients were treated with a flexible dose of haloperidol in a 5-week study. The neuroleptic blood levels of all patients were measured; however, for 10 of the patients, the treating physician remained blind to the drug blood level. The Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions (CGI) scale were administered at study entry and once a week by a blind rater. No clinical differences were seen between the two groups at any time point. However, blood levels within an operative therapeutic range of 10-20 ng/ml were seen at the same rate in both groups of patients. These data do not contradict other findings which suggest a correlation between clinical outcome and blood level but rather suggest that responsible clinicians using clinical signs can maintain the "average patient" within the range of therapeutic blood levels, even without the laboratory monitoring of such levels.