<abstract xmlns="http://www.w3.org/1999/xhtml">

<bold>Objective.</bold> The aim of the present study was to investigate the presence of inflammatory mediators in rats with only periodontitis and periodontitis in a setting of hyper- and hypo-thyroidism and to analyze the correlative linkages between inflammatory mediators and thyroid hormones.
<bold>Methods.</bold> White male 12–14 weeks old inbred rats (n=48) weighing 180–200 g were employed in the experiment. They were randomly divided into the following groups: Group I – control group, Group II – group with a model of periodontitis, Group III – group with a periodontitis in a setting of hyperthyroidism, and Group IV – group with periodontitis in a setting of hypothyroidism. The presence of tumor-necrosis factor-α (TNF-α) and interleukins IL-1β and IL-10 in the periodontal homogenate supernatant was studied by a solid-phase enzyme-linked immunosorbent assay.
<bold>Results.</bold> It was shown that experimental lipopolysaccharide (LPS)-induced periodontitis is accompanied by hyperproduction of pro-inflammatory cytokines (TNF-α, IL-1β) and reduction of anti-inflammatory cytokines (IL-10), whereas TNF-α underwent to maximum changes. Thyroid dysfunction exacerbates cytokine imbalance and severity of inflammation in experimental LPS-induced periodontitis, especially pronounced at hyperthyroidism, as evidenced by the predominance of TNF-α and IL-1β levels in the periodontal homogenate supernatant by 38.5% (р&lt;0.01) and 75.6% (p&lt;0.001), respectively, hyperthyroid over the euthyroid, and by 20.1% (p&lt;0.05) and 24.1% (p&lt;0.05), respectively, over the hypothyroid rats.
<bold>Conclusions.</bold> Thyroid dysfunction, especially hyperthyroidism, may play an important role in the pro-inflammatory response in periodontitis. Hyperproduction of inflammatory mediators in thyroid dysfunction can induce a noticeable damage in the whole apparatus of the periodontium, thereby causing progression of periodontitis.
</abstract>

Does thyroid dysfunction influence inflammatory mediators in experimental periodontitis?

<abstract xmlns="http://www.w3.org/1999/xhtml">

<bold>Objective.</bold> Emerging data indicate that oxidative stress is closely associated with the pathogenesis of cardiovascular disease in type 2 diabetes mellitus (T2DM). The present study aimed to assess the effect of the most abundant flavonoid in the human diet quercetin (Q) on the myocardial redox status in rats with T2DM.
<bold>Methods.</bold> T2DM was induced in male Wistar rats by a high caloric diet (for 14 weeks) and two streptozotocin (25 mg/kg b.w.) injections applied in four weeks of the diet, once a week for two weeks. The Q was administered intragastrically by gavage in a dose of 10 or 50 mg/kg of the body weight for 8 weeks starting from the 8th day after the last streptozotocin injection. The control rats received citrate buffer and seven days after the last STZ injection, basal glucose levels were measured in all animals.
<bold>Results.</bold> Administration of Q increased insulin sensitivity in diabetic rats with more pronounced effect at a dose of 50 mg/kg b.w. The Q also decreased free radical oxidation in the heart mitochondria of diabetic animals, thus limiting the formation of advanced oxidation protein products in a dose-dependent manner and normalized the activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, glutathione reductase) in cardiac mitochondria independently of the dose used. In addition, the Q in both doses prevented the development of oxidative stress in the T2DM rats cardiomyocytes by reducing NADPH oxidase and xanthine oxidase activities.
<bold>Conclusions.</bold> The findings demonstrate that Q in both doses 10 mg/kg and 50 mg/kg can protect from the development of oxidative stress in cardiomyocytes in the diabetic rats. The present data indicate that the use of Q may contribute to the amelioration of cardiovascular risk in patients with T2DM.
</abstract>

V. N. Karazin Kharkiv National University

Quercetin improves myocardial redox status in rats with type 2 diabetes

<abstract xmlns="http://www.w3.org/1999/xhtml">

<bold>Objective.</bold> Changes in the brain derived neurotrophic factor (BDNF) and glucocorticoid receptor (GR) expression in the prefrontal cortex (PFC) and hippocampus (HIP) are associated with psychiatric diseases and stress response. Chronic mild stress (CMS) may alter BDNF as well as GR levels in both the PFC and the HIP. The aim of the present study was to find out whether chronic treatment with a typical antipsychotic haloperidol (HAL) and an atypical antipsychotic aripiprazole (ARI) may modify the CMS effect on the BDNF and GR expression in the above-mentioned structures.
<bold>Methods.</bold> The rats were exposed to CMS for 3 weeks and from the 7th day of CMS injected with vehicle (VEH), HAL (1 mg/kg) or ARI (10 mg/kg) for 4 weeks. BDNF and GR mRNA levels were established in the PFC and the HIP by Real Time PCR, whereas, PFC and HIP samples were obtained by punching them from 500 µm thick frozen sections. C-Fos immunoreactivity was analyzed in the PFC and the HIP on 30 µm thick paraformaldehyde fixed sections. Weight gain and corticosterone (CORT) levels were also measured.
<bold>Results.</bold> The CMS and HAL suppressed the BDNF and GR mRNA levels in the PFC. In the HIP, CMS elevated BDNF mRNA levels that were suppressed by HAL and ARI treatments. The CMS decreased the c-Fos immunoreactivity in the PFC in both HAL- and ARI-treated animals. In the HIP, HAL increased the c-Fos immunoreactivity that was again diminished in animals exposed to CMS. Stressed animals gained markedly less weight until the 7th day of CMS, however, later their weight gain did not differ from the unstressed ones or was even higher in CMS+HAL group. Un-stressed HAL and ARI animals gained less weight than the VEH ones. Neither CMS nor HAL/ARI affected the plasma CORT levels.
<bold>Conclusion.</bold> The present data indicate that HAL and ARI in the doses 1 mg/kg or 10 mg/kg, respectively, does not modify the effect of the CMS preconditioning on the BDNF and GR mRNA levels in the PFC or the HIP. However, HAL seems to modify the CMS effect on the HIP activation.
</abstract>

Haloperidol and aripiprazole impact on the BDNF and glucocorticoid receptor levels in the rat hippocampus and prefrontal cortex: effect of the chronic mild stress

<abstract xmlns="http://www.w3.org/1999/xhtml">

<bold>Objective.</bold> Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by chronic hypophosphatemia and osteomalacia. We present case of a patient with a protracted clinical course of TIO. TIO profoundly affected every aspect of his life with subsequent profound physical and psychosocial disabilities.
<bold>Method.</bold> The review of a complex clinical presentation, serial laboratory investigations, and imaging modalities of a patient with TIO caused by a mesenchymal tumor.
<bold>Results.</bold> The patient presented with chronic lower back pain, severe bilateral leg weakness, and multiple pathological fractures due to severe osteoporosis. His investigations revealed hypophosphatemia, low 1,25 dihydroxyvitamin D, phosphaturia and normal serum calcium, and parathyroid hormone. Elevated fibroblast growth factor 23 (FGF23) confirmed the diagnosis of TIO and 68Ga-DOTATATE-positron emission tomography/computed tomography (PET/CT) imaging correctly identified a tumor in the left femoral head. His clinical features and biochemical abnormalities promptly recovered after successful surgical resection of the mesenchymal tumor.
<bold>Conclusion.</bold> The present case demonstrated the need to extensively investigate causes of generalized bone pain in patients with hypophosphatemia, as TIO is highly curable. Importantly, 68Ga-DOTATATE PET/CT imaging successfully identified the FGF23 producing tumor, which was undetectable by conventional imaging, favoring its early use in suspected TIO presentation. The present report highlights the importance of timely diagnosis of this complex medical condition, aiming to improve general awareness and enable better clinical outcomes for this rare disorder.
</abstract>

Tumor-induced osteomalacia – a mystery illness beyond aches, pains, and depression

<abstract xmlns="http://www.w3.org/1999/xhtml">

<bold>Objectives.</bold> Immune reconstitution therapies (IRT), which include antibody-based cell-depleting therapies targeting CD52+ (alemtuzumab) or CD20+ (rituximab, ocrelizumab) leukocytes, are approved for the treatment of multiple sclerosis. Thyroid autoimmunity is a common adverse effect of alemtuzumab treatment, Graves’ disease (GD) being the most prevalent manifestation. To date, thyroid autoimmunity events have not been reported with CD20-targeting monoclonal antibodies.
<bold>Case Report.</bold> A 59-year-old woman with primary progressive multiple sclerosis with no prior personal history of thyroid disease or autoimmunity, was diagnosed with GD 6 months following the first ocrelizumab infusion. She was asymptomatic and had no signs of ophthalmopathy. Due to the temporal association of GD diagnosis with ocrelizumab infusion, absence of symptoms and our experience with alemtuzumab-induced GD, we decided for an active surveillance strategy and antithyroid drugs were not started. She underwent spontaneous resolution of hyperthyroidism with thyroid-stimulating hormone (TSH) receptor antibodies (TRAb) negativity and a mild and transitory period of subclinical hypothyroidism, while she continued the biannually ocrelizumab administration schedule. To present date, she has maintained close clinical and biochemical surveillance with normal TSH, free thyroxine (fT4) and free triiodothyronine (fT3) levels and undetectable TRAb.
<bold>Conclusions.</bold> This is the first case of GD reported after ocrelizumab administration. The timing, onset and course of this case is similar to alemtuzumab-induced GD, usually interpreted as an “immune reconstitution syndrome”; however, ocrelizumab cell count depletion is inferior in severity, cell population affected and duration of depletion. This case highlights the importance of pre-screening and follow-up with thyroid function tests in patients treated with ocrelizumab. As a novel therapeutic antibody, further investigation is required to unravel the causes of thyroid autoimmunity.
</abstract>

Department of Endocrinology, Diabetes and Metabolism

Centro Hospitalar e Universitario do Porto

Graves’ disease with spontaneous resolution following ocrelizumab in primary progressive multiple sclerosis

<abstract xmlns="http://www.w3.org/1999/xhtml">

The pathophysiology of COVID comprises an exaggerated pro-inflammatory response. Hypothalamic-pituitary-adrenal (HPA) axis has a crucial role in various inflammatory conditions and modulated immunological response. Limited evidence is available regarding the incidence and the effect of HPA dysfunction in COVID-19. Although the cortisol levels have only been estimated in a few studies, the dehydroepiandrosterone sulfate (DHEAS) release from the adrenal gland has not been explored yet. In this mini review, the authors discuss the role of dehydroepiandrosterone (DHEA) and DHEAS in the acute stress response and immunological modulation. Various effects of DHEAS have been demonstrated in different diseases. The specific inhibitory effect of DHEA on interleukin 6 (IL-6) could be of paramount importance in COVID-19. Further, DHEA supplementation has already been proposed in inflammatory conditions, like rheumatoid arthritis. DHEAS levels in COVID-19 may help to understand the HPA axis dysfunction as well as the possibility of repurposing DHEA as a drug for mitigating the pro-inflammatory COVID-19.
</abstract>

Does dehydroepiandrosterone sulfate have a role in COVID-19 prognosis and treatment?

<abstract xmlns="http://www.w3.org/1999/xhtml">

<bold>Objectives.</bold> This review assesses the comparative safety and efficacy of selected 3-hydroxy-3-methylglutaric acid coenzyme A inhibitors (statins, cinnamic acids. 3-hydroxy-3-methyl glutaric acid) on the pre-onset type 2 diabetes (PT2D) and post-onset type 2 diabetes (T2D)-related cluster of seven features (central obesity, hyperglycemia, hypertension, dyslipidemia, pro-thrombosis, oxidation and inflammation).
<bold>Methods.</bold> Google scholar and PubMed were searched for statin*, flaxseed lignan complex (FLC), cinnamic acid (CA)*, and 3-hydroxy-3-methylglutaric acid (HMGA) in conjunction with each of PT2D, T2D and the cluster of seven. An introduction was followed by findings or absence thereof on the impacts of each of statins, FLC, CAs and HMGA on each member of the cluster of seven.
<bold>Results.</bold> Pravastatin manages three features in PT2D, while a number of the statins improve five in T2D. FLC is negative in PT2D but controls four in T2D; it is not clear if the CAs and HMGA in FLC play a role in this success. CAs have potential in six and HMGA has potential in three of the cluster of seven though yet CAs and HMGA are untested in PT2D and T2D in humans. There are safety concerns with some statins and HMGA but FLC and CAs appear safe in the doses and durations tested.
<bold>Conclusions.</bold> Selected statins, FLC, CAs and HMGA can manage or have a potential to manage at least three features of the cluster of seven. Most of the literature-stated concerns are with select statins but there are concerns (one actual and two potential) with HMGA.
</abstract>

Selected 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors. A look into their use and potential in pre-diabetes and type 2 diabetes

AHEAD OF PRINT

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