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Aldosterone rapidly activates p-PKC delta and GPR30 but suppresses p-PKC epsilon protein levels in rat kidney

Abstract

Objectives. Aldosterone rapidly enhances protein kinase C (PKC) alpha and beta1 proteins in the rat kidney. The G protein-coupled receptor 30 (GPR30)-mediated PKC pathway is involved in the inhibition of the potassium channel in HEK-239 cells. GPR30 mediates rapid actions of aldosterone in vitro. There are no reports available regarding the aldosterone action on other PKC isoforms and GPR30 proteins in vivo. The aim of the present study was to examine rapid actions of aldosterone on protein levels of phosphorylated PKC (p-PKC) delta, p-PKC epsilon, and GPR30 simultaneously in the rat kidney.

Methods. Male Wistar rats were intraperitoneally injected with normal saline solution or aldosterone (150 µg/kg body weight). After 30 minutes, abundance and immunoreactivity of p-PKC delta, p-PKC epsilon, and GPR30 were determined by Western blot analysis and immunohisto-chemistry, respectively.

Results. Aldosterone administration significantly increased the renal protein abundance of p-PKC delta by 80% (p<0.01) and decreased p-PKC epsilon protein by 50% (p<0.05). Aldosterone injection enhanced protein immunoreactivity of p-PKC delta but suppressed p-PKC epsilon protein intensity in both kidney cortex and medulla. Protein abundance of GPR30 was elevated by aldosterone treatment (p<0.05), whereas the immunoreactivity was obviously changed in the kidney cortex and inner medulla. Aldosterone translocated p-PKC delta and GPR30 proteins to the brush border membrane of proximal convoluted tubules.

Conclusions. This is the first in vivo study simultaneously demonstrating that aldosterone administration rapidly elevates protein abundance of p-PKC delta and GPR30, while p-PKC epsilon protein is suppressed in rat kidney. The stimulation of p-PKC delta protein levels by aldosterone may be involved in the activation of GPR30.

Open access
Efficacy and safety of dulaglutide in patients with absolute insulin deficiency

Abstract

Objective. While dulaglutide has been approved inpatients with type 2 diabetes (T2DM) in combination with insulin, it has not been studied in insulin-deficient patients, not whether they have type 1 diabetes (T1DM) or T2DM. The aim of this study is to assess the efficacy and safety of dulaglutide 0.75 mg/once weekly (QW) in patients with absolute insulin deficiency (n=10).

Subjects and Results. Significant reductions of HbA1c (9.30±1.03% to 8.61±1.21%; p<0.02) and body mass index (BMI; 23.61±3.95 to 23.41±4.24; p<0.02) levels were observed at 3 months with the addition of dulaglutide to the existing pharmacotherapy. However, in all the patients, post-meal C-peptide levels remained undetectable. One patient had gastrointestinal adverse events and discontinue dulaglutide within the first month. One patient was a non-responder, who had little if any changes in HbA1c levels at 3 months.

Conclusions. The results indicate that dulaglutide is effective in patients with T1DM or T2DM with absolute insulin deficiency, though gastrointestinal adverse events might be of concern. The improvements in glycemic control could not be due to enhanced insulin secretion, but may be as a result of a combination of the other effects of glucagon like peptide 1 (GLP-1), such as postprandial glucagon suppression, delayed gastric emptying, and weight loss.

Open access
Implantation and pregnancy outcome of Sprague-Dawley rats exposed to pirimiphos-methyl

Abstract

Objective. This study was designed to investigate the effect of sublethal doses (10, 60, and 120 mg/kg of pirimiphos-methyl on implantation and pregnancy in female Sprague-Dawley rats. Pirimiphos-methyl is a pesticide widely used worldwide, especially in Africa to protect food against pests and has gained widespread acceptance.

Methods. Pregnant Sprague-Dawley rats used for this study had access to food and water ad libitum and were divided into a control group and three experimental groups based on dose of chemical given. The pregnant rats were given pirimiphos-methyl orally on days 1–5, 1–7, 7–18th day of gestation and from day 1 to term. Implantation studies were carried out on days 6 and 8 of pregnancy, while the fetal parameters were ascertained on day 19 of pregnancy and at term. Serum levels of progesterone and estradiol were measured on days 6, 8 and 19 of pregnancy.

Results. Sublethal administration of pirimiphos-methyl showed decreased number of implantation sites on days 6 and 8, fetal weight, crown-to-rump length, length of umbilical cord and placenta weight (day 19), birth weight, litter size and total number (at term) in rats administered with pirimiphos-methyl when compared with control.

Conclusion. Administration of pirimiphos-methyl resulted in a reduced implantation rate due to decreased uterine receptivity caused by an imbalance in the level of estradiol and progesterone and impaired reproductive outcome during pregnancy.

Open access
Pheochromocytoma

Abstract

Pheochromocytomas are rare tumors originating in the adrenal medulla. They may be sporadic or in the context of a hereditary syndrome. A considerable number of pheochromocytomas carry germline or somatic gene mutations, which are inherited in the autosomal dominant way. All patients should undergo genetic testing. Symptoms are due to catecholamines over production or to a mass effect. Diagnosis is confirmed by raised plasma or urine metanephrines or normetanephrines. Radiology assists in the tumor location and any local invasion or metastasis. All the patients should have preoperative preparation with α-blockers and/or other medications to control hypertension, arrhythmia, and volume expansion. Surgery is the definitive treatment. Follow up should be life-long.

Open access
Sex and salt intake dependent renin-angiotensin plasticity in the liver of the rat

Abstract

Objective. Epidemiological studies confirm that hypertensive patients respond differently to renin-angiotensin system (RAS) inhibition depending on their gender. The aim of present work is to focus on sex-dependent differences in RAS regulation under conditions of increased salt intake.

Method. To investigate RAS, we measured the expression of angiotensinogen (Agt) mRNA, angiotensin receptor type 1 (AT1) mRNA and mitochondria assembly receptor (MasR) in the liver of rats under control conditions and after feeding with a salt diet (2% NaCl). In parallel, vascular endothelial growth factor A (VEGF-A) mRNA was analyzed.

Results. Regression analysis revealed sex-dependent differences in the correlation between mRNA expression of AT1 and that of Agt, MasR and VEGF-A in both groups. There was a significant negative correlation between AT1 and Agt mRNA expression in the male control group, but this correlation disappeared in males exposed to a salt diet. In females, AT1 and Agt expression correlated only in the group exposed to the salt diet. In control males, there was a borderline trend to correlation between AT1 and MasR mRNA expression. The correlation between AT1 and VEGF-A mRNA expression was significant only in the control females, however, after exposure to a salt diet, this correlation diminished.

Conclusions. We hypothesize that RAS components expression is compensated differently in males and females. The observed loss of compensatory relationships in RAS between AT1 and Agt and AT1 and MasR in male rats under a salt diet can contribute to the differences observed in human with hypertension associated with an unhealthy diet.

Open access
Spatial relationship between the c-Fos distribution and enkephalinergic, substance P, and tyrosine hydroxylase innervation fields after acute treatment with neuroleptics olanzapine, amisulpride, quetiapine, and aripiprazole in the rat septum

Abstract

Objective. The aim of the present study was to demonstrate the spatial relationship between the c-Fos immunoreactive cells elicited by an acute treatment with neuroleptics including amisulpride (AMI), olanzapine (OLA), quetiapine (QUE), and aripiprazole (ARI) and enkephalinergic (ENK), substance P (SP), and tyrosine hydroxylase (TH) innervation fields in the rat septum.

Methods. Male Sprague Dawley rats received a single injection of OLA (5 mg), ARI (10 mg), AMI (20 mg), QUE (15 mg/kg/b.w.). Ninety min after antipsychotics administration, the animals were transcardially perfused with a fixative and the brains 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 endproduct. Afterwards, the sections were exposed to ENK, SP, and TH antibodies and the reaction product visualized by biotin-labeled fluorescent AlexaFluor 564 dye. The data were evaluated from the sections either simultaneously illuminated with fluorescent and transmission microscope beams or after merging the separately illuminated sections in the Adobe Photoshop 7.0 software.

Results. ENK, SP, and TH displayed characteristic spatial images formed by a dense accumulation of immunoreactive fibers and terminals on the both sides of the septum. A dense plexus of axons formed by ENK and SP immunopositive terminals were situated predominantly in the lateral, while TH ones more medial portion of the septum. QUE and AMI activated distinct amount of c-Fos expression in cells located within the SP-immunoreactive principal innervation field. The OLA effect on the c-Fos expression was very pronounced in the ventral TH-labeled principal innervation field including the space between the ENK field ventral portion and the dorsal margin of the accumbens nucleus shell. Generally, the occurrence of c-Fos cells in the ENK-immunoreactive principal innervation field, in comparison with the surrounding septal area, was less abundant after all of the four antipsychotics treatments.

Conclusion. The data of the present study indicate that ENK, SP, and TH innervation fields may influence separate populations of septal cells activated by AMI, OLA, QUE, and ARI and that each of these region-differently innervated cells may be associated with the functional heterogeneity of the individual lateral septal nuclei.

Open access
Ulmus minor bark hydro-alcoholic extract ameliorates histological parameters and testosterone level in an experimental model of PCOS rats

Abstract

Objective. Polycystic ovary syndrome (PCOS) is a common and multifactorial disease associated with female factor infertility. Ulmus minor bark (UMB) is one of the medicinal plants used in Persian folklore as a fertility enhancer. In the current study, we aimed to elucidate the effect of UMB hydro-alcoholic extract on histological parameters and testosterone condition in an experimental model of PCOS rats.

Methods. Thirty female rats were randomly divided into five groups: (1) control, (2) vehicle, (3) PCOS/50 mg [6 mg/kg dehydroepiandrosterone (DHEA) + 50 mg/kg UMB hydro-alcoholic extract], (4) PCOS/150 mg (6 mg/kg DHEA + 150 mg/kg UMB hydro-alcoholic extract), and (5) PCOS (6 mg/kg DHEA). All interventions were performed for 21 days. Afterwards, stereological analysis was done for determination of ovarian volume and follicle number. The serum level of testosterone was measured by ELISA kit.

Results. UMB hydro-alcoholic extract improved the total number of the corpus luteum in the treatment groups when compared to the PCOS group (p<0.05). PCOS/150 mg and PCOS/50 mg groups showed significantly lower total number of the primordial, primary, and secondary follicles as well as testosterone level compared to the PCOS group (p<0.05). The total number of antral follicles and volume of ovary did not differ significantly between groups.

Conclusion. UMB extract may be an effective and good alternative in improving PCOS histo-logical and testosterone disturbances although further studies are warranted to confirm the safety of UMB plant in human.

Open access
Disease perception and coping strategies for stress in Polish patients with various mental disorders

Abstract

Introduction: Nowadays more and more people struggle with mental problems associated with fast pace of life and overpowering stress. Individuals affected by mental disorders frequently apply ineffective methods of coping with stress, and their attitudes towards the disease in fact strengthen the psychopathological symptoms. The purpose of the present study was to compare disease perception and coping strategies for stress in Polish patients with various types of mental disorders.

Material and Methods: The study involved 123 patients with depressive disorders, anxiety disorders, schizophrenia, alcohol related disorders, subjects detained due to psychoactive substance-induced psychotic disorders and amnestic syndromes, staying at Mental Healthcare Centre. Measurements of the variables were carried out using COPE Inventory and Disease Perception Questionnaire.

Results: The type of mental disorder differentiated the group with respect to the use of strategies aimed at seeking instrumental and emotional support, planning, positive reinterpretation, focus on emotions and substance use. There are significant differences between patients in the approach to illness as a task, weakness and threat.

Conclusions: The results show that the type of mental disorder is important in the context of the strategies used for coping with stress and the patients' approach to their condition.

Open access
Dissociative identity disorder as a wide range of defense mechanisms in children with a history of early childhood trauma

Abstract

Introduction: Dissociative identity disorder, also known as multiple personality disorder, involves simultaneous manifestation of multiple alternative personalities in one human body. The disorder is still a puzzle to contemporary researchers. In comparison to the United States, where the detection rate of this disorder is growing, in Poland, it is still a niche issue, unknown to many scientists and clinicians. Rather alarmingly, this situation has remained the same for many years now.

Objective: The aim of the present study is to draw attention to the adaptive character of dissociative identity disorder as a defense mechanism in children who have experienced extremely traumatic events in early childhood. The work also sets itself the task of disseminating knowledge about multiple personality disorder in the Polish scientific community, with the hope of encouraging wider research in this area in Poland.

Material and Methods: To investigate this issue, we searched articles available in the PubMed, Google Scholar, and Polish Medical Bibliography (Polska Bibliografia Lekarska) databases for the years 1960–2018. The following search terms were used: multiple personality, dissociative identity disorder, dissociative identity disorder and children. On the basis of a meta-analysis of the available literature, we offer a general characterization of the disorder, describe its symptomatology, present several theories of its etiology and conclude it through the prism of its adaptive function.

Results and Discussion: From the analysis of the gather data, we can conclude that multiple personality disorder can be a broad variant of the child's defense mechanisms against extreme, traumatic events from childhood, which they try to cope with by creating alter personalities. Abused children create other representations of the Self to be able to rid themselves of suffering, a process that is necessary for them to survive and further develop mentally and physically.

Conclusions: There is no doubt that Polish research on this disorder is much needed. It could provide more information on the epidemiology, diagnosis, and treatment of multiple personality. In addition, a better understanding of the issue might bring us closer to the understanding of how the human mind works.

Open access
Kleptomania in a 15-year-old boy with ADHD – a case report

Abstract

Aim: The aim of the study was 1) to report the case of a 15-year-old boy who developed kleptomania symptoms during methylphenidate treatment and 2) to review the available therapeutic options for kleptomania based on a literature search of Medline and Google Scholar databases (2000–2018).

Case report: For the past seven years a 15-year-old boy had participated in counselling at a psychological counselling centre because of school problems and upbringing difficulties, and had a five-year history of psychiatric treatment for ADHD. He was admitted to the Department of Psychiatry because of recurrent stealing episodes that occurred during methylphenidate treatment. During the hospitalization, the patient did not observe the therapeutic contract – he stole items from other patients. Pharmacotheraputic and psychotherapeutic treatment resulted in a partial improvement in impulsive behaviour. At discharge, he spoke critically of his previous conduct and expressed readiness to continue treatment in an outpatient setting.

Conclusions:

  1. Kleptomania has a very negative impact on a patient's overall well-being.
  2. In the reported case, kleptomania developed during methylphenidate treatment.
  3. Kleptomania should always be taken into account as a possible cause of stealing during a psychiatric examination, to avoid stigmatization of patients as criminals.
  4. Pharmacotherapy and cognitive-behavioural psychotherapy focused on the development of strategies, which can help the patient to control the urge to steal, are important components of kleptomania treatment.

Open access