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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
CD4/CD8 Antibodies Reduce Histopathological Damage in Salivary Glands of Spontaneously Diabetic Mice

Abstract

Background and aims: Diabetes affects the metabolism promoting damage in different tissues, including salivary glands. Current treatments, such as insulin, are ineffective to recovery of these tissues. In this aspect, the immunotherapy has been tested, but it can be inefficient as an agent for the control of damage caused by diabetes. The aim of this study to evaluate the association in anti-CD4 and anti-CD8 monoclonal antibody in the recovery of salivary glands of diabetic NOD mice.

Material and methods: Fifteen spontaneously diabetic mice (NOD) were divided into three groups with 5 animals each: group I (Balb/C control mice), group II (untreated NOD mice), group III (NOD mice treated with CD4 and CD8 antibodies). The CD4 and CD8 antibodies (IMUNY, Rheabiotech Ltda, Brazil) were administered by intravenously injections (25 ug/days: 0, 7, 14, and 21). After treatment salivary glands samples were analyzed by immunofluorescence, microscopy, light microscopy and stereology. (ethical approval process: 304/11), Analysis of variance (ANOVA) and Kruskal-Wallis nonparametric test were used.

Results: Elevated levels of glucose (mg/dl) were observed in untreated animals (group II) (605.25 ± 31.23, p≤0.05), whereas in treated animals (group III), were noted a decrease in these levels (464.77 ± 39.66, p≤0.05). Tissue restructure, characterized by cell volume recovery, also was observed in group III (nuclear volume of parotid glands: (109.91 ± 02.03, p≤0.05) and submandibular glands: (107.52 ± 02, p≤0.05) (cytoplasmic volume of parotid glands: (356.14 ± 26.34, p≤0.05) and submandibular glands: (331.22 ± 32.11, p≤0.05). Intense signaling (+++) of insulin receptors was observed in animals of group I. On the other hand, in group II was noted a reduction of these receptors (+). In treated animals (group III) were observed a recovery of the insulin receptors (+++).

Conclusions: This treatment was effective in the recovery of salivary acinar cells, contributed also to homeostasis of body metabolism. Thus, this immunomodulation promoted a beneficial effect on the recovery of these tissues.

Open access
Epidemiology of Dyslipidemia Among Adult Population of Bangladesh

Abstract

Background and aims: evatedEl level serum of lipids stimulate atherosclerosis, which is the risk factor for stroke, peripheral vascular taeohrrratrrocvtra disease. The aim of this study was to explore the pattern and associated factors of dyslipidemia among Bangladeshi adult population.

Material and methods: A descriptive cross-sectional study was conducted at the outpatient department (OPD) of four Medical College Hospitals, Bangladesh. 200 adults aged 20 to 65 years diagnosed case of dyslipidemia were randomly selected. Fasting CHO, HDL, LDL and TG were measured. According to the criteria of the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III), dyslipidemia was classified into (a) Hyper-lipidemia: TC>200 mg/dl, TG>150 mg/dl, (b) Hyper cholesterolemia: TC>200 mg/dl, (c) Hyper-triglyceridemia: TG>150 mg/dl, and (d) Atherogenic-dyslipidemia: TG>150 mg/dl, LDLC>165 mg/dl.

Results: Study found 46% hyperlipidemia, 37% atherogenic dyslipidemia, 13.5% hypercholesterolemia and only 3.5% hypertriglyceridemia. BMI, FBS and HDL-C were significantly higher among female compare to male (p=<0.01, <0.01 and 0.04 respectively). TC and TG were significantly higher among higher calorie intake group in compare to normal intake group (p=0.04).

Conclusions: Results of this study concluded that hyperlipidemia and atherogenic dyslipidemia are common and female dyslipidemic patients are susceptible to develop higher BMI, FBS, and HDL-C.

Open access
Evaluation of Pancreatic and Extra Pancreatic Effects of Branched Amino Acids

Abstract

Background and aims: Leucine, Isoleucine, and Valine collectively known as Branched-chain amino acids (BCAAs), can be closely associated with metabolic dysregulates and with insulin resistance. We aimed to explore the role of BCAAs as potential treatment option for diabetes.

Material and method: Bioassay the effect of BCAAs on MIN6 cell line on insulin secretion and pancreatic beta cells expansion, then were checked for inhibitory potential of pancreatic amylase, glucosidase and lipase as alternative approach for diabetes treatment.

Results: BCAAs significantly enhance insulin secretion parallel to L-alanine efficacy. Furthermore, BCAAs obtain a dose dependent β-cell proliferation similar to glucagon-like peptide-1. Moreover, these acids could restore the secretory function of MIN6 β-cell despite stressful gluco-lipo-toxicity; separately or combined. Moreover, BCAAs exerted a dose dependent dual inhibition of amylase, glucosidase and lipase.

Conclusions: Our current findings suggest that BCAAs supplementation may have a potential therapeutic effect against diabetes as insulin releasing agent and as specific inhibitors for both-amylase/α-amyloglucoside and lipase

Open access
Gender-Specific Differences of Oxidative Processes in the Population of Circulating Neutrophils of Rats in a Setting of Prolonged Administration of Monosodium Glutamate

Abstract

Background and aims: Monosodium salt of glutamic acid (MSG) is one of the most common food additives. The aim of study was to assess, in gender-specific terms, how prolonged administration of MSG effects on reactive oxygen and nitrogen species formation and the apoptotic/necrotic processes in the population of rats circulating neutrophils.

Material and methods: Experimental studies were conducted on 32 mature white rats. MSG was administered intragastrical at a dose of 30 mg/kg body weight for 30 days. The analysis of cell samples to determine neutrophils with overproduction of reactive oxygen species (ROS) and signs of apoptosis\necrosis was evaluated with flow laser cytometry method. The total nitric oxide synthase (NOS) activity was determined by monitoring the rate of conversion of L-arginine into citrulline. The total quantity of NO metabolites was assessed by evaluating of nitrite and nitrate ions.

Results: We found a significant increase in generation of ROS, intensification of nitroxydergic processes, an increase in the percentage of apoptotic neutrophils and no changes in the percentage of necrotic neutrophils.

Conclusions: We observed activation of oxidative and nitroxydergic processes in rats with prolonged administration of MSG, which initiate apoptosis. In gender-specific terms, a more pronounced changes were seen in male rats.

Open access