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Objectives. The purpose of the present paper is to propose and introduce novel biomarkers of autoimmune polyendocrine syndromes that are relevant to the early diagnosis and optimal medical management of the patients who already suffer from type 1 diabetes mellitus.

Methods. We hypothesize and demonstrate on a case study that various organ-specific autoimmune endocrinopathies can result in lowered basal insulin requirements, leading to unexplained hypoglycemia.

Results. It can be hypothesized that hypothyroidism in patients with type 1 diabetes mellitus may deteriorate glycemic control and can lead to an increased rate of hypoglycemia, particularly the overnight and morning hypoglycemia. Thus, the decreased requirements for particularly overnight basal insulin can be an early marker of the autoimmune polyendocrine syndrome-3 with subclinical autoimmune thyroiditis in immune-mediated type 1 diabetes mellitus. Further, it could be proposed that unexplained hypoglycemia during the late afternoon or evening could be an early marker of the autoimmune polyendocrine syndrome-2 with subclinical autoimmune Addison disease in immune-mediated type 1 diabetes mellitus. As a result, an altered circadian pattern of basal insulin requirements can occur, characterized by a decreased late afternoon basal insulin rate.

Conclusions. After exclusion of other causes, the unexplained reoccurring hypoglycemia can be a remarkable feature of autoimmune polyendocrine syndromes in immune-mediated type 1 diabetes mellitus on intensive insulin replacement therapy.


Objective. Pregnancy can cause diabetic conditions and gestational diabetes is the most common metabolic disorder of the era. Scientific evidence suggests that obesity increases the incidence and severity of gestational diabetes. Adipokines are proteins secreted from adipose tissue in response to extracellular stimuli and altered metabolism. These hormones are involved in regulating the energy balance, lipid metabolism, and insulin sensitivity. One of the types of adipokines is called adiponectin, which has anti-diabetic, anti-inflammatory, and anti-atherogenic effects. Accordingly, this study is aimed to investigate the correlation between the serum adiponectin level with the gestational diabetes and the postpartum metabolic syndrome.

Methods. This case-control study was carried out on 37 pregnant women (in Sari, Iran) with gestational diabetes and 37 non-diabetic pregnant women who were matched regarding age and body mass index (BMI). Serum adiponectin and glucose levels were measured. Finally, six weeks after termination of pregnancy, women in both groups were evaluated for metabolic syndrome. All statistical analyses of this study were performed using IBM SPSS software version 21 and, in all cases, the two-way p value less than 0.05 was considered statistically significant.

Results. The mean age of pregnant women was 28.46±4.11 years in the non-diabetic group and 30.03±4.71 in the diabetic group. There was no statistically significant difference found between the mean age (p=0.123) and BMI (p=0.727) in two groups. Serum adiponectin levels in the diabetic group (5.51±3.15 µg/ml) were significantly lower than in the non-diabetic group (8.35±4.54 µg/ml) (p=0.003). In the diabetic group, serum adiponectin level did not correlate with the maternal age, maternal BMI, and postpartum metabolic syndrome (p>0.005).

Conclusions. The results of the present study indicate a correlation of low adiponectin concentrations with gestational diabetes, but this association with postpartum metabolic syndrome is uncertain. However, to elucidate the mechanism of adiponectin in predicting gestational diabetes and postpartum metabolic syndrome further studies are required.


Objective. The vast majority of type 1 diabetes leads to a higher prevalence of reproductive system’s impairments. Troxerutin has attracted much attention owing to its favorable properties, including antihyperglycemic, anti-inflammatory, and antiapoptotic effects. This investigation was proposed to evaluate whether pretreatment with troxerutin could prevent apoptosis-induced testicular disorders in prepubertal diabetic rats.

Methods. Fifty prepubertal male Wistar rats were randomly allocated into five groups: control (C), troxerutin (TX), diabetic (D), diabetic+troxerutin (DTX), and diabetic+insulin (DI). Diabetes was induced by 55 mg/kg of streptozotocin applied intraperitoneally. In TX and DTX groups, 150 mg/kg troxerutin was administered by oral gavage. Diabetic rats in DI group received 2–4 U NPH insulin subcutaneously. Troxerutin and insulin treatments were begun immediately on the day of diabetes confirmation. After 30 days, the testicular lipid peroxidation and antioxidant activity, apoptosis process, and stereology as well as serum glucose and insulin levels were assessed.

Results. The results showed that diabetes caused a significant increase in the blood glucose, the number of TUNEL positive cells and tubules, and the malondialdehyde level as well as a significant decrease in serum insulin level compared to controls. The stereological analysis also revealed various alterations in diabetic rats compared to controls. Troxerutin treatment improved these alterations compared to the diabetic group.

Conclusion. Troxerutin-pretreatment may play an essential role in the management of the type-1 diabetes-induced testicular disorders by decreasing blood glucose and modulating apoptosis.


Objective. The goal of this study was to reveal the impact of four types of atypical antipsychotics including amisulpride (AMI), olanzapine (OLA), quetiapine (QUE), and aripiprazole (ARI), with different receptor-affinity profile and dissociation constant, on the activity of hypothalamic supraoptic nucleus (SON) vasopressinergic and oxytocinergic neurons.

Methods. Male Sprague Dawley rats received a single injection of vehicle (VEH) (0.1 ml/100g), AMI (20 mg/kg), OLA (5 mg/kg), QUE (15 mg/kg/) or ARI (10 mg/kg). Ninety min after treatment, the animals were fixed by transcardial perfusion, the brains removed, and cryocut into serial coronal sections of 35 µm thickness. The sections were processed for c-Fos staining using an avidin-biotin-peroxidase complex and visualized by nickel intensified diaminobenzidine to reach black end product. Afterwards, the sections were exposed to vasopressin (AVP) and oxytocin (OXY) antibodies and the reaction product visualized by biotin-labeled fluorescent Alexa Fluor 568 dye. The data were evaluated from c-Fos and AVP or OXY merged sections.

Results. The present study shows that all four antipsychotics applied induced c-Fos expression in the SON. With respect to the stimulation efficacy of the individual antipsychotics, estimated based on the quantity of c-Fos-labeled AVP and OXY neurons, could be a preferential action assigned to QUE over moderate effect of ARI and lower effect to OLA and reduced effect of AMI (VEH < AMI < OLA < ARI < QUE).

Conclusion. The present data for the first time provide an insight into the quantitative pattern of brain activity within the clusters of SON AVP and OXY cells in response to different atypical antipsychotics single treatment.


Objectives. Psychoactive drugs are group of compounds used to treat severe mental problems, including psychosis, as well as other conditions. This study assessed clinically relevant side effects of haloperidol and clozapine on the thyroid hormones.

Methods. Haloperidol (0.05 and 2 mg/kg) or clozapine (0.5 and 20 mg/kg) was intraperitoneally injected to male Wistar rats for 28 days. The control group received 2 ml of physiological saline. A chemiluminescent immunoassay was used to measure the plasma levels of thyroid hormones.

Results. Plasma concentrations of thyroxine (T4) in rats treated with high-dose (2 mg/kg) of haloperidol decreased significantly compared to the control group (p=0.001). However, both low (0.5 mg/kg) and high clozapine (20 mg/kg) doses did not have a significant effect on the plasma concentrations of T4 and triiodothyronine (T3) (p>0.05). Neither of the compound had a significant effect on T3 plasma concentration levels (p>0.05).

Conclusions. Haloperidol and clozapine act via different mechanisms and may have dissociable effects on thyroid hormones. Following treatment with haloperidol, significant changes in T4, but not in T3, serum levels were observed. Haloperidol and clozapine had different effects on the thyroid hormone levels. These results indicate that antipsychotic treatment can contribute to the thyroid dysfunction. Therefore, greater caution should be applied to the antipsychotics use. The thyroid function of the patients should be closely monitored, while using these drugs.


Objective. The exact mechanism, by which spinal cord injury (SCI) leads to a male subfertility is not well-known. Present study was conducted to determine the mechanisms that lead to the elevated end-product cytokines and inflammasomes in the testes of an SCI rat model. Moreover, we evaluated the inflammasome components following SCI in testis over a defined time periods.

Methods. Weight drop technique was used to induce SCI at the level of the T10 vertebra in male Wistar rats. The animals were sacrificed at specific time intervals (3, 7, 14, 21, and 28 day’s post-SCI). mRNA levels of inflammasomes and cytokines were measured by real-time PCR, germ cells apoptosis was evaluated by TUNEL staining, and the epithelium of seminiferous tubules by Miller’s and Johnsen’s scores.

Results. The results showed activation of Nlrp3 in the testes of SCI animals at different time points. Expression of Nlrp3 and IL-1β sharply increased 14 days after the SCI. Upregulation of IL-1β and IL-18 at days 14 and 21 post-SCI might disintegrate the epithelium of seminiferous tubules at day 14 and induce germ cells apoptosis, increase abnormal sperm cells, and attenuate motility and viability at 21 days post-SCI.

Conclusion. This study provided further evidence of innate immunity activation in testes that could lead to more disruption of spermatogenesis in SCI patients at specific times.


Objective. Thyroid hormones have important actions in the adult brain. They regulate genes expression in myelination, differentiation of neuronal and glial cells, and neuronal viability and function.

Methods. We used the pathway-specific real-time PCR array (Neurotrophins and Receptors RT2 Profiler PCR Array, QIAGEN, Germany) to identify and verify nerve impulse transmission pathway-focused genes expression in peripheral white blood cells of patients with postoperative hypothyroidism, hypothyroidism as a result of autoimmune thyroiditis (AIT) and AIT with elevated serum an anti-thyroglobulin (anti-Tg) and anti-thyroid peroxidase (anti-TPO) antibodies.

Results. It was shown that patients with postoperative hypothyroidism and hypothyroidism resulting from AIT had significantly lower expression of BDNF and CBLN1. In patients with AIT with elevated serum anti-Tg and anti-TPO antibodies, the expression of GDNF was significantly down-regulated and the expression of PNOC was up-regulated. The expression levels of MEF2C and NTSR1 were decreased in the group of patients with postoperative hypothyroidism and AIT, correspondingly.

Conclusions. The results of this study demonstrate that AIT and hypothyroidism can affect the expression of mRNA nerve impulse transmission genes in gene specific manner and that these changes in gene expressions can be playing a role in the development of neurological complications associated with thyroid pathology. Detection of the transcriptional activity of nerve impulse transmission genes in peripheral white blood cells can be used as an important minimally invasive prognostic marker of the risk for developing neurological complications comorbid with thyroid pathology.


Objectives. This review assesses the polypharmacy reduction potential of cinnamic acids (CAs) and some related compounds in managing three or more of the cluster of seven, pre- and post-type 2 diabetes mellitus (T2DM)-related features (central obesity, hyperglycemia, hypertension, dyslipidemia, pro-thrombosis, oxidation, and inflammation).

Methods. Google scholar and Pubmed were searched for cinnam*, chlorogenic acid, ferulic acid, and caffeic acid in conjunction with each of pre- and post-onset T2DM, central obesity, hyperglycemia, hypertension, dyslipidemia, pro-thrombosis, oxidation, and inflammation. The study was divided into an introduction followed by findings on the impacts of each of the CAs including trans-CA acid, the E isomer of a CA-based thiazolidinedione and a metabolite of that isomer, as well as p-methoxy CA, various cinnamic amides and some other CA-related compounds (chlorogenic acid, cinnamaldehyde, ferulic and caffeic acid).

Results. Trans-CA has a potential to manage three, while each of chlorogenic acid, cinnamalde-hyde, caffeic acid and ferulic acid has a potential to manage all seven members of the cluster. Other CA-related compounds identified may manage only one or two of the cluster of seven.

Conclusions. Much of the work has been done in animal models of pre- and post-onset T2DM and non-pre- or post-onset T2DM humans and animals, along with some cell culture and in vitro work. Very little work has been done with human pre- and post-onset T2DM. While there is potential for managing 3 or more members of the cluster with many of these compounds, a definitive answer awaits large pre- and post-T2DM onset clinical trials with humans.


Objectives. Fibromatosis is a rare tumor with a prevalence of 2–4 per million per year. Its occur-rence in the thyroid is very rare and to the best of our knowledge only five cases have been reported in the literature.

Subject and Results. In this case report, we present a thirty-seven-year-old man without any significant past medical history, who presented with an anterior neck swelling and occasional cough for four months before admission. Sonographic-guided fine needle aspiration cytology studies reported a follicular neoplasm. Microscopic and immunohistochemical evaluation of the thyroidectomy specimen showed thyroid fibromatosis. The patient had no symptoms after surgery and no signs of recurrence after 2 years of follow-up.


Objective. Olanzapine (OLA), amisulpride (AMI), aripiprazole (ARI), and quetiapine (QUE) belong to antipsychotics, which administration represents still most reliable way for the treatment of schizophrenic and bipolar disorders. The intention of the present study was to explore whether the acute administration of a particular antipsychotic, indicated by the presence of c-Fos, will: a) stimulate neurons already activated by a long lasting homogeneous or heterogeneous stress preconditioning, indicated by the FosB/ΔFosB (ΔFosB) expression, or b) have a stimulatory effect only on a not activated, so called silent neurons. The pattern of ΔFosB and c-Fos spatial relationship was investigated in three forebrain structures, including the septal ventrolateral nucleus (seVL), the striatal dorsolateral area (stDL), and the shell of the nucleus accumbens (shell).

Methods. The rats were divided into 10 groups and exposed to two types of stressors. Half of them was exposed to a sequence of homogeneous stressor – handling (HDL) and the other half to a heterogeneous stressor (CMS) daily for 20 days. CMS consisted of five types of stressors: crowding, air-puff, wet bedding, predator stress, and forced swimming applied in an unexpected order. On the 21st day of the experiment, the rats were free of the stress exposure and on the 22nd day, both groups of animals receive a single intraperitoneal injection of vehicle (4% DMSO in saline, 0.1 ml/100 g) or OLA (5 mg/kg), AMI (20 mg/kg), ARI (10 mg/kg), and QUE (15 mg/kg). 90 min after the drugs administration the animals were transcardially perfused, brains removed, cut into 30 µm thick coronal sections, and double stained: first with ΔFosB antibody linked with Alexa488 fluorescent dye and second with c-Fos antibody linked to Alexa596 one. Quantitative evaluation of ΔFosB and c-Fos colocalizations was performed on fluorescence photomicrographs transformed into a final picture containing only yellow, green, and red colored circles.

Results. The data of this investigation demonstrate that ΔFosB and c-Fos colocalizations occurred in each of the three areas investigated, i.e. seVL, stDL, and shell ones, in both HDL as well as CMS preconditioned rats. The levels of ΔFosB and c-Fos colocalizations varied in the individual forebrain areas studied. From the total 22 areas measured, level of c-Fos colocalization prevailed over ΔFosB in 18 ones. However, neither c-Fos nor ΔFosB reached 100% level of colocalization in any of the forebrain areas investigated.

Conclusion. The present findings indicate that ΔFosB and c-Fos colocalizations occurred in each of the three areas investigated, i.e. seVL, stDL, and shell, in both HDL and CMS preconditioned rats, whereas the parallel occurrence of free c-Fos as well as c-Fos colocalized with ΔFosB might speak out for a possible involvement of the c-Fos activated by antipsychotics applied in dual, i.e. short- and long-lasting, functions.