Effect of Intraoperative Propofol-Induced Sedation on the Neurotransmitter Levels (Pilot Study)

The aim of the study was to determine the changes in the levels of various neurotransmitters depending on the depth of propofol-induced sedation.Material and methods. Twenty-four patients were included in a prospective, simple blinded study. All patients underwent elective orthopedic intervention with subarachnoid anesthesia and moderate (group 1, n=12) or deep (group 2, n=12) propofol-induced sedation. Peripheral blood sampling for measurement of neurotransmitter levels was performed before regional blockade (Stage 1), 35–40 min after the start of sedation (Stage 2), and 10–15 min after sedation was terminated and consciousness was recovered (Stage 3).Results. Deep propofol-induced sedation resulted in a decrease in norepinephrine level at stages 2 and 3. Under moderate sedation, its level decreased at Stage 2 and returned to baseline after restoration of consciousness. The initial concentration of norepinephrine (Stage 1) was higher in Group 2.Conclusion. Propofol-induced sedation resulted in reduced level of the main stress hormone, which suggests its stabilizing effect on autonomic nervous system.

Analytic and Integrative Framework for Understanding Human Sympathetic Arterial Baroreflex Function: Equilibrium Diagram of Arterial Pressure and Plasma Norepinephrine Level

BackgroundThe sympathetic arterial baroreflex is a closed-loop feedback system for stabilizing arterial pressure (AP). Identification of unique functions of the closed system in humans is a challenge. Here we propose an analytic and integrative framework for identifying a static operating point and open-loop gain to characterize sympathetic arterial baroreflex in humans.Methods and ResultsAn equilibrium diagram with two crossing functions of mechanoneural (MN) and neuromechanical (NM) arcs was analyzed during graded tilt maneuvers in seven healthy subjects. AP and plasma norepinephrine level (PNE), as a surrogate for sympathetic nerve activity, and were recorded after vagal modulation of heart function was blocked by atropine. The MN-arc curve was described as a locus of operating points during –7, 0, 15, and 60° head-up tilting (HUT) on a PNE-AP plane. The NM-arc curve was drawn as a line between operating points before and after ganglionic blockade (trimethaphan, 0.1 mg⋅ml–1⋅kg–1) during 0° or 15° HUT. Gain values were estimated from the slopes of these functional curves. Finally, an open-loop gain, which is a most important index for performance of arterial baroreflex, was given by a product of the gain values of MN (GMN) and NM arcs (GNM). Gain values of MN was 8.92 ± 3.07 pg⋅ml−1⋅mmHg−1; and GNM at 0° and 15° HUT were 0.61 ± 0.08 and 0.36 ± 0.05 mmHg⋅ml⋅pg–1, respectively. A postural change from supine to 15° HUT significantly reduced the open-loop gain from 5.62 ± 0.98 to 3.75 ± 0.62. The effects of HUT on the NM arc and open-loop gain seemed to be similar to those of blood loss observed in our previous animal studies.ConclusionAn equilibrium-diagram analysis contributes to a quantitative and integrative understanding of function of human sympathetic arterial baroreflex.

High Norepinephrine Status Induced Growth of Colorectal Cancer With Type 2 Diabetes Mellitus Benefited From ADP-Ribosyltransferase 1

BackgroundIt is known that type 2 diabetes mellitus patients have higher susceptibility to colorectal cancer and poorer prognosis, but the mechanism is quite unknown. Here, we investigated effect of ADP-Ribosyltransferase 1 on growth of colorectal cancer combined diabetes in high norepinephrine status and the potential mechanism. MethodsWe evaluated size and weight of transplanted tumors with different ADP-Ribosyltransferase 1 level of CT26 cells or different norepinephrine level on diabetic mice model and observed their survival time as well. Consistently, CCK8 and flow cytometry were applied for detecting growth of CT26 cells in vitro. Western blot was performed for analyzing differentially expressed proteins of proliferatic profiles to determine ADP-Ribosyltransferase 1-modulated pathway.ResultsAccording to our data, high level of norepinephrine and ADP-Ribosyltransferase 1 both facilitated proliferation of CT26 cells in vitro and in vivo, besides, inhibition of norepinephrinee-depended-proliferation was observed in ADP-Ribosyltransferase 1 silencing CT26 cells in vitro compared with CT26 cells with ADP-Ribosyltransferase 1 expression. However, we discovered after reducing norepinephrine level of serum by surgery, size and weight of the transplanted tumors were significantly reduced compared with non-operated group and sham-operated group. Further, expression of ADP-Ribosyltransferase 1, mTOR, STAT3, p-AKT protein in tumor tissues of diabetic mice was increased rather than non-diabetes mice, while after depleting norepinephrine level by renal denervation operation, expression of proliferation-relative proteins mTOR, STAT3, p-AKT protein was decreased, but no change was discovered in ADP-Ribosyltransferase 1 expression. While under the same concentration of norepinephrine environment, ADP-Ribosyltransferase 1 boosts expression of p-AKT, mTOR, STAT3, CyclinD1 and c-myc in CT26 cells in vitro. ConclusionsThis study proposed a hypothesis that high-norepinephrine-induced proliferation of colorectal cancer required expression of ADP-Ribosyltransferase 1, and raise ADP-Ribosyltransferase 1 might be a candidate target for treatment of diabetes-associated colorectal cancer.

Adrenal Incidentaloma: Challenges in Diagnosing Adrenal Myelolipoma

Adrenal myelolipomas (AMLs) are rare benign adrenal tumors, containing adipose and hematopoietic tissue, a result of reticuloendothelial cell metaplasia. Incidence on autopsy has been reported from 0.08% to 0.4%. AMLs are generally considered nonsecretory. The functional aspect of adrenal incidentaloma should be evaluated. In this article, we report a case of a 40-year-old male, who presented with uncontrolled hypertension and renal failure, with imaging revealing an adrenal incidentaloma. He was started on dialysis for acute fluid overload, and workup for pheochromocytoma revealed an elevated serum norepinephrine level of 1181 pg/mL. Free metanephrine and normetanephrine levels were low when checked pre- and post-dialysis. Complete resection of the encapsulated right adrenal mass was performed. Pathology of the adrenal tumor demonstrates an 11.5 × 9.5 × 7.5 cm well-circumscribed, partially encapsulated proliferation of mature adipose tissue with admixed hemopoietic elements consistent with myelolipoma weighing 29.3 g. This case highlights the inclusion of a full metabolic workup for all adrenal incidentalomas, including AML.

Angiogenic properties of catecholamines from the viewpoint of the pathogenesis of retinopathy of prematurity

Purpose: to assess the level of catecholamines norepinephrine and dopamine in rat retina with experimental retinopathy of prematurity (EROP) at a time corresponding to the peak of neovascularization.Material and methods. The study was performed on 41 infant Wistar rats (82 eyes). The rats were divided into 2 groups: the experimental group (with EROP, n = 21) and the control group (n = 20). In order to reproduce the EROP, the newborn rats were placed for 14 days in the incubator together with their mother. Every 12 hours, the oxygen concentration in the incubator ranged from 60 to 15 %. The control group consisted of pups who were held in conditions with a normal oxygen content (21 %) from the moment of birth. The pups were withdrawn from the experiment on the 10th, 14th, 23rd and 28th day, whereupon they were subjected to binocular enucleation followed by histological examination, in addition, the content of noradrenaline and one of the metabolites of dopamine (L-DOPA) was determined in retinal samples of the eyeballs obtained on the 23rd day by highly effective liquid chromatography technique with electrochemical detection.Results. Histological examination showed that in our EROP model the neovascularization peak occurs on the 23rd day of the experiment. At this time rat pups with EROP showed a significantly lower retinal L-DOPA level as compared to the control values (13.99 ng/g and 30.5 ng/g, respectively), and the norepinephrine level significantly exceeded such values (63.7 ng/g and 7.69 ng/g, respectively).Conclusion. A relative deficiency of dopamine and a relative excess of norepinephrine of the rat pups with EROP is noted at the time of the highest vascular activity of the retina. The obtained data confirm anti-angiogenic properties of dopamine and pro-angiogenic properties of noradrenaline in the second phase of EROP development.

Is Tadpole Pupil in an Adolescent Girl Caused by Denervation Hypersensitivity?

Tadpole pupil is a rarely encountered phenomenon caused by episodic, segmental iris dilator muscle spasm of short duration (2–15 minutes), occurring in clusters without a known precipitating factor. It has most commonly been described in women aged 28 to 48 years. A few hypotheses on pathogenesis have been discussed but none has been proved. Here, we present an adolescent girl with bilateral tadpole pupil that appeared during physical exercise. This is the first pediatric case of tadpole pupil, not caused by preceding surgery, to be published. Based on (1) this case in which tadpole pupil developed when the norepinephrine level rose during exercise, (2) the high ratio of patients with tadpole pupil who concurrently have or later develop Horner syndrome, in which denervation hypersensitivity is well described, (3) a previous report of a patient with both tadpole pupil and Horner syndrome who had denervation hypersensitivity on pharmacological testing, (4) a 29-year-old man with unilateral tadpole pupil induced by exercise, and (5) a 19-year-old man with bilateral tadpole pupil and possible autonomic neuropathy, we suggest denervation hypersensitivity as a probable pathogenic mechanism causing tadpole pupil. In addition, a suggestion for investigations to be performed in future pediatric cases is provided.

Impact of Exposure to Fenitrothion on Vital Organs in Rats

This study was designed to investigate the impact of oral administration of fenitrothion (10 mg/kg) on liver, kidney, brain, and lung function in rats. The effect was studied on days 7, 14, 21, 28, and 42. Our results have shown deterioration in liver function as evidenced by the elevation in serum ALT, AST, ALP, and bilirubin and reduction in albumin and hepatic glycogen. This was associated with a state of hyperglycemia and hyperlipidemia and increased prothrombin time, while hemoglobin content was reduced. In addition, the kidney function was reduced as indicated by the elevation in serum creatinine, uric acid, and BUN, while the serum levels of magnesium, potassium, and sodium were reduced. This study also showed an impairment in brain neurotransmitter (elevated 5-HT, glutamate, GABA, and reduced dopamine and norepinephrine level). This was associated with a reduction in the barrier capacity in brain and lung. Fenitrothion also caused a decrease in cholinesterase activity in serum, lung, and brain activity associated with a state of oxidative stress in all tested organs and hyperammonemia. These results support the hazards of pesticide use and shows the importance of minimizing pesticide use or discovering new safe pesticides.