Analysis of density changes of selected brain receptors after a 14-day supply of chromium(III) and evaluation of chromium(III) affinity to selected receptors and transporters

Chromium(III) is one of the most controversial biometals. Although, it is no longer on the list of minerals necessary for the proper functioning of the human body, and its pharmacological effect is still under discussion. One of the purposes of Cr(III) administration is to use it in patients with mood disorders and it is strictly related to its pharmacological, not dietary effect. This is because its high doses are necessary to obtain the results and additionally, no deficiencies in human population have been noted. In this study, the affinity of chromium(III) to selected receptors and transporters in the rat brain was evaluated, and the effect of the 14-day administration of thismetal was assessed on the density of selected receptors. All analyses were performed in vitro using radioligand binding assays, and the results indicated lack of affinity to β1 and α1 receptors and serotonin transporter (SERT), furthermore very weak affinity to the 5-HT1A receptor (30% inhibition at 10−4 and 10−5 M). Analysis of the α1 and β1 adrenergic receptor density indicated lack of any adaptive effects after 14 days of Cr(III) administration through intraperitoneal injections (doses 6 and 12 mg/kg). The antidepressant activity of chromium(III) indicated in clinical trials concerned patients with atypical, seasonal, or dystonic symptoms. This effect, as it seems based on the presented results, does not depend on direct affinity to serotonin receptors and transporter nor is the result of adaptive changes in the adrenoreceptor system

Zinc Deficiency and Depression

Zinc deficiency has multiple effects, including neurological and somatic symptoms. Zinc deficiency can lead to depression, increased anxiety, irritability, emotional instability, and induced deficits in social behavior. Clinical studies have shown that low levels of zinc intake contributes to the symptoms of depression and patients suffering from depression have a lower serum zinc level. Also the animal studies have shown an important role of dietary zinc deficiency in the induction of depressive‐like symptoms. Moreover, both preclinical and clinical studies have indicated the potential benefits of zinc supplementation as an adjunct to conventional antidepressant drugs or as a stand‐alone intervention. This chapter focuses on the role of the zinc deficiency in the pathogenesis of depression, changes in animal behavior induced by dietary zinc restriction, the role of zinc supplementation in the treatment of depression, and the possible mechanisms involved in these relationships. Both clinical and preclinical studies related to these findings will be discussed

Ketamine and Ro 25-6981 reverse behaviorala abnormalities in rats subjected to dietary zinc restriction

Clinical and preclinical studies indicate that zinc (Zn) is an essential factor in the development and treatment of major depressive disorder (MDD). Conventional monoamine-based antidepressants mobilize zinc in the blood and brain of depressed patients as well as rodents. N-methyl-D-aspartate acid receptor (NMDAR) antagonists exhibit antidepressant-like activity. However, not much is known about the antidepressant efficacy of NMDAR antagonists in zinc-deficient (ZnD) animals. We evaluated the antidepressant-like activity of two NMDAR antagonists (ketamine; global NMDAR antagonist and Ro 25-6981 (Ro); selective antagonist of the GluN2B NMDAR subunit) in ZnD rats using the forced swim test (FST) and sucrose intake test (SIT). A single dose of either Ro 25-6981 or ketamine normalized depressive-like behaviors in ZnD rats; however, Ro was effective in both tests, while ketamine was only effective in the FST. Additionally, we investigated the mechanism of antidepressant action of Ro at the molecular (analysis of protein expression by Western blotting) and anatomical (density of dendritic spines by Golgi Cox-staining) levels. ZnD rats exhibited decreased phosphorylation of the p70S6K protein, and enhanced density of dendritic spines in the prefrontal cortex (PFC) compared to control rats. The antidepressant-like activity of Ro was associated with the increased phosphorylation of p70S6K and ERK in the PFC. In summary, single doses of the NMDAR antagonists ketamine and Ro exhibited antidepressant-like activity in the ZnD animal model of depression. Animals were only deprived of Zn for 4 weeks and the biochemical effects of Zn deprivation and Ro were investigated in the PFC and hippocampus. The shorter duration of dietary Zn restriction may be a limitation of the study. However, future studies with longer durations of dietary Zn restriction, as well as the investigation of multiple brain structures, are encouraged as a supplement to this study

Analysis of selected methods of diagnostics and physiotherapy of pes plano-valgus in children

Introduction: Flat feet is one of the most common posture defects among children and it usually co-occurs with valgus of the heels, which is called pes plano-valgus. There are many diagnostic methods and physiotherapeutic activities that allow for early detection and appropriate correction of the defect. The use of non-surgical methods may allow the child to avoid surgery in the future. Aim and Methods: Review and analysis of the current scientific literature on the diagnosis and physiotherapy of plano-valgus feet in children. Conclusions: In the diagnostic process, there are many static and dynamic methods for the assessment of plano-valgus foot among children. Special devices such as plantoconturograph, podoscope, and pedobarographic mat are used in the diagnosis of feet in children and have proven to be helpful in the detailed analysis of foot defects. However, an extensive range of physiotherapeutic methods allows for comprehensive treatment using not only corrective exercises, but also physical therapy treatments in order to relieve pain and accelerate recovery. Orthopedic appliances, such as supination insoles, also play an important role in the treatment. The best results were seen in the use of comprehensive treatment and multiple terapeutic methods. Early detection and correct diagnosis of foot abnormalities allow for appropriate treatment with the use of a wide range of physiotherapy methods. This increases the chances of restoring normal foot functions among children and reducing pain with other abnormal symptoms

Evaluation of anti-inflammatory and ulcerogenic potential of zinc-ibuprofen and zinc-naproxen complexes in rats

Because of numerous indications and high availability, non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed and used medicines in the world. However, long-term therapy with and improper use of NSAIDs may lead to gastrointestinal damage. Therefore, improving the therapeutic index of the existing drugs has become a priority over the past decades. Considerable attention in the field has been concentrated on metal complexes of non-steroidal anti-inflammatory drugs. The aim of this study is to evaluate the effect of complexation with zinc on the anti-inflammatory and ulcerogenic effects of ibuprofen and naproxen after single and triple intragastric administration to rats. The anti-inflammatory effect was assessed in carrageenan-induced inflammatory edema in the hind paw of male albino Wistar rats. The mucosal lesions were inspected and evaluated for gross pathology. Single administration of both the investigated complexes, namely zinc-ibuprofen and zinc-naproxen (20 mg/kg equivalent to ibuprofen and naproxen, respectively) and their parent drugs and physical mixtures with zinc hydroaspartate (ZHA doses: 16.05 and 14.37 mg/kg), caused a significant reduction of the edema after the same time from the carrageenan injection in comparison to the control groups. However, no statistically significant differences between the investigated drugs were observed after their single administration. The mean ulceration score for the mixture of ibuprofen and ZHA was statistically lower than the mean score achieved in rats after treatment with ibuprofen alone. On the other hand, triple intragastric administration of the ZHA-ibuprofen and ZHA- naproxen combination showed substantial enhancement of the anti-inflammatory activity against control groups, as well as against the parent NSAIDs. The most potent anti-inflammatory activity was demonstrated after 2 h from the carrageenan injection in animals receiving ZHA together with naproxen. The edema growth was reduced in these animals by 80.9% as compared to the control group. This result was significantly higher than the results achieved in animals receiving zinc-naproxen (50.2%) or naproxen alone (47.9%). Both NSAID complexes with zinc and mixtures with ZHA alleviated ulcerations caused by parent NSAIDs; however, the mixtures of both ibuprofen and naproxen with ZHA after triple administration were the least damaging. In view of the above results, zinc supplementation during NSAID therapy may have a beneficial effect on ulcer prevention and healing by reducing the effective dose of the parent drug and increasing its potency

Serotonin transporter activity of imidazolidine-2,4-dione and imidazo[2,1-f]purine-2,4-dione derivatives in aspect of their acid–base properties

Affinities of arylpiperazinylalkyl derivatives of imidazo[2,1-f]purine-2,4-dione and imidazolidine-2,4-dione for serotonin transporter and their acid–base properties were evaluated. The dissociation constant (pK(a)) of compounds 1–22 were determinated by potentiometric titration and calculated using pKalc 3.1 module of the Pallas system. The data from experimental methods and computational calculations were compared and suitable conclusions were reached