Role of serotonin in development of esophageal and gastric fundal varices

AIM:To determine the effect of free serotonin concentrations in plasma on development of esophageal and gastric fundal varices. METHODS:This prospective study included 33 patients with liver cirrhosis and 24 healthy controls. Ultrasonography and measurement of serotonin concentration in plasma were carried out in both groups of subjects. The upper fiber panendoscopy was performed only in patients with liver cirrhosis. RESULTS:The mean plasma free serotonin levels were much higher in liver cirrhosis patients than in healthy controls (219.0 ± 24.2 nmol/L vs 65.4 ± 18.7 nmol/L,P < 0.0001). There was no significant correlation be-tween serotonin concentration in plasma and the size of the esophageal varices according to Spearman coefficient of correlation (rs =-0.217,P > 0.05). However,the correlation of plasma serotonin concentration and gastric fundal varices was highly significant (rs =-0.601,P < 0.01). CONCLUSION:Free serotonin is significant in pathogenesis of portal hypertension especially in development of fundal varices,indicating the clinical value of serotonergic receptor blockers in these patients.     

Daidzein administration positively affects thyroid C cells and bone structure in orchidectomized middle-aged rats

Summary

Thyroid C cells hormone, calcitonine, inhibits bone resorption. We have demonstrated that daidzein treatment of orchidectomized rats (model for osteoporosis) stimulated C cells and increased trabecular bone mass. These results suggest that, besides direct action, daidzein may also affect bone structure indirectly through enhancement of thyroid C cell activity.

Introduction

Thyroid C cells produce calcitonin (CT) which acts as an inhibitor of bone resorption. In this study, the influence of daidzein treatment on thyroid C cells, bone structure, and bone function in orchidectomized (Orx) middle-aged rats was investigated.

Methods

Sixteen-month-old Wistar rats were divided into Orx and sham-operated (SO) groups. Half the Orx rats were given subcutaneous injections of daidzein (30 mg/kg b.w./day) for 3 weeks. CT-immunopositive thyroid C cells were morphometrically analyzed. The metaphyseal region of the proximal tibia was measured histomorphometrically, and cancellous bone area (B.Ar), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp) were calculated. Serum samples were analyzed for CT and osteocalcin (OC), calcium (Ca) and phosphorus concentrations, and urine samples for Ca levels.

Results

Treatment of Orx animals with daidzein significantly increased volume of C cells compared to the Orx rats. Daidzein also enhanced B.Ar, Tb.Th, and Tb.N and reduced Tb.Sp. The serum OC and urinary Ca concentrations decreased significantly in comparison with the Orx group.

Conclusions

These findings indicate that daidzein treatment stimulates thyroid C cells, increase trabecular bone mass, and decrease bone turnover in Orx middle-aged rats, which is the model of male osteoporosis.     

Subclinical left ventricular echocardiographic abnormalities 1 year after kidney transplantation are associated with graft function and future cardiovascular events

Cardiovascular events (CVE) are the leading cause of mortality in kidney transplant recipients. Increased left ventricular mass (LVM) is a risk factor for CVE. This study investigated the associations of LVM with impaired kidney graft function expressed as lower glomerular filtration rate (GFR) at 1 year after transplantation and future CVE beyond 1 year. The prospective study cohort included 68 nondiabetic recipients of a kidney transplant between January 2004 and December 2005 who underwent a transthoracic echocardiographic investigation at 1 year after transplantation. LVM and left ventricular hypertrophy (LVH) were assessed using 2-dimensional M-mode echocardiography. GFR was estimated (eGFR) by the 4-variable Modification of Diet in Renal Disease formula. Cox proportional hazards analysis was used to estimate cardiac CVE (angina pectoris, acute myocardial infarct, coronary angioplasty or bypass surgery, or sudden cardiac death) hazard ratios (HRs) for patients with LVH versus control subjects with no LVH at 1 year after transplantation. All patients had normal systolic function (ejection fraction >50%) with no symptoms or signs of heart failure. LVH was present in 44 patients (65%). LVM and incidence of LVH were increased in 28 patients with eGFR <60 mL/min/1.73 m² compared with 40 patients with eGFR ≥60 mL/min/1.73 m² (248 ± 61 g and 86% vs 210 ± 46 g and 50%, respectively; P < .01). After a median follow-up of 4.5 years, there were 18 (26.5%) cardiac CVE. The incidence of CVE was higher in patients with LVH than in patients with no LVH at 1 year after transplantation (36.4% vs 8.3%; P = .020). In adjusted analyses, LVH was associated with an increased risk for future CVE (HR, 4.69; 95% confidence interval, 1.02–21.5; P = .037). In kidney transplant recipients, a lower eGFR at 1 year after transplantation was associated with greater LVM and higher incidence of LVH. Presence of LVH was associated with an increased risk for future CVE.     

Dentinal hypersensitivity following scaling and root planing: comparison of low-level laser and topical fluoride treatment

The aim of this study is to compare the effectiveness of low-level laser irradiation to traditional topical fluoride treatment for treatment choices of dentinal hypersensitivity following scaling and root planing. The experimental group (15 patients) was treated with low-energy-level diode laser at each site of dentinal hypersensitivity following scaling and root planning. The control group (15 patients) received topical fluoride treatment (protective varnish for desensitization). All the patients were treated at baseline visit, and then at day 2 and 4 after the initial treatment; the pain was subjectively assessed by the patients as strong, medium, medium low, low, or no pain. Total absence of the dental hypersensitivity was reported in 26.66% of the examined group even after the second visit, compared to the control group where complete resolution of the hypersensitivity was not present after the second visit in any of the treated cases. Complete absence of pain was achieved in 86.6% of patients treated with laser and only in 26.6% in the fluoride treated group, after the third visit. Based on our findings, we conclude that low-energy biostimulative laser treatment can be successfully used for treatment of dental hypersensitivity following scaling and root planing.     

A three-dimensional evaluation of microleakage of class V cavities prepared by the very short pulse mode of the erbium:yttrium–aluminium–garnet laser

The aim of this study was to evaluate microleakage along resin restoration in cavities prepared with an erbium:yttrium–aluminium–garnet (Er:YAG) laser, with and without acid etching, and to compare it with that in diamond-drilled cavities. Thirty intact molars were divided into three equal groups. In the teeth in group I, class V cavities were prepared with a diamond drill. Cavities in groups II and III were prepared with an Er:YAG laser (400 mJ/15 Hz for enamel and 250 mJ/10 Hz for dentine). The cavities in groups I and II were acid-etched and adhesive and flowable composite were applied to all cavities. The specimens were first immersed in dye for 24 h and then in 5% nitric acid for 72 h for softening. The fillings were extracted and photographed through a dissecting microscope. The leakage area was measured with specially designed software. The Kruskal–Wallis test showed that the best ranking was group II [mean range (m.r.) = 27.46], followed by group I (m.r. = 33.48) and, lastly, group III (m.r. = 45.15). The differences between groups I and III (P = 0.023) and between groups II and III were statistically significant (P = 0.080). The least microleakage was found in those cavities prepared by Er:YAG laser and subsequently acid-etched, whereas the most leakage was in the lased cavities that had not been etched; the traditional diamond-drilled acid-etched cavities produced medium leakage.     

Abnormal fatty acid distribution of the serum phospholipids of patients with non-Hodgkin lymphoma

The data about the fatty acid (FA) status of non-Hodgkin lymphoma (NHL) patients are poor. Therefore, the aim of this study was to investigate the FA profile of serum phospholipids in NHL patients related to the aggressiveness and clinical stage of NHL. We analyzed the FA profile of serum phospholipids in 47 newly diagnosed, untreated NHL patients and in 29 healthy subjects. Significantly higher (p?<?0.001) levels of palmitic (16:0), oleic (18:1 n-9) and arachidonic acids (20:4 n-6), saturated and monounsaturated FA were found in NHL patients, while linoleic acid (18:2 n-6) and the levels of total polyunsaturated FA (PUFA), n-3 PUFA, eicosapentaenoic (20:5 n-3) and docosahexaenoic (DHA, 22:6 n-3) were significantly reduced (p?<?0.01). The level of oleic acid in patients with indolent NHL was significantly lower (p?<?0.05) than in more aggressive types of disease. Contents of palmitoleic acid, docosatetraenoic (22:4 n-6), and PUFA was lower in very aggressive NHL. According to clinical stage (CS), patients with CS I had significantly higher SFA and lower n-6 FA than other three groups, and group with CS IV showed significantly decreased DHA and n-3 PUFA. Our results showed an abnormal FA profile in serum phospholipids in NHL patients.     

Age-associated plasticity of α1-adrenoceptor-mediated tuning of T-cell development

Alpha₁-adrenoceptors (α₁-ARs) are involved in neuro-thymic and thymic intercellular communications, and consequently modulation of T-cell development. Ageing is associated with a number of changes in noradrenergic neuro-effector transmission, and possibly intercellular noradrenaline (NA)-mediated communication resulting in altered responses of target cells to NA. Thus, in old animals an altered NA modulation of thymopoiesis via α₁-ARs may be expected. To test this hypothesis, in old and young adult Wistar rats we examined: 1) thymic NA levels, density of noradrenergic innervation and NA synthesizing cells, as well as α₁-AR expression, and 2) then the effects of 14-day-long treatment with the α₁-AR blocker, urapidil, on thymocyte development. Overall, the first part of study suggested augmented NA signalling to thymic cells via α₁-ARs due to increased NA availability and α₁-AR thymocyte surface density in old rats. The second part of study supported this assumption. Namely, although in rats of both ages urapidil affected the same thymocyte developmental steps ultimately leading to changes in the relative number of the most mature single positive TCRαβ^high thymocytes, its effects were generally more prominent in old animals. Following urapidil treatment, the percentages of CD4 + CD8− cells, including those showing a regulatory CD4 + CD25 + RT6.1− phenotype, were increased, while CD4 − CD8+ cells decreased. In old rats, an augmented thymic escape of immature CD4 + CD8+ cells was also registered. In rats of both ages the thymic changes were accompanied by alterations in the proportions of major cell populations in the T-lymphocyte compartment of both peripheral blood and spleen, leading to an increase in the CD4+/CD8+ T-cell ratio. These alterations were also more pronounced in old rats. Moreover, in old rats following urapidil treatment the proportion of TCRαβ + cells in the periphery was slightly greater reflecting, most likely, partly enhanced thymic production of regulatory CD161 + TCRαβ + cells. Thus, the study indirectly suggests an age-associated increase in the basal α₁-AR-mediated inhibitory influence of NA on thymopoiesis.     

Lecithin/chitosan nanoparticles for transdermal delivery of melatonin

In this study, the potential of lecithin/chitosan nanoparticles (NPs) as colloidal nanosystem for transdermal melatonin delivery was investigated. Mean diameter and zeta-potential of NPs differing in lecithin type (Lipoid S45 and S100) and chitosan content ranged between 113.7 and 331.5?nm and 4.6 and 31.2?mV, respectively. Melatonin loadings were up to 7.2%. The potential of lecithin/chitosan NPs to enhance transdermal melatonin delivery was investigated by determining the drug flux across dermatomed porcine skin and its skin deposition. Lecithin/chitosan NPs provided 1.3-2.3-fold higher flux compared to melatonin solution. The highest flux, 9.0?±?0.21?μg/cm2/h, was observed for S45 lecithin/chitosan NPs with lecithin/chitosan weight ratio of 20:1. NP possible cytotoxicity in vitro was evaluated using human skin keratinocytes and fibroblasts. It was demonstrated that lecithin/chitosan NPs can be applied to skin cells at concentrations up to 200?μg/mL without inducing plasma membrane damage or cell viability decrease.     

Impact of different antidopaminergic mechanisms on the dopaminergic control of prolactin secretion

Antipsychotics are the most common cause of pharmacologically induced hyperprolactinemia. Although this adverse effect was the subject of numerous observations, the mechanisms and promotive factors were not completely investigated yet. Increased awareness of clinical consequences of hyperprolactinemia implicates the necessity for further examinations. The aim of this randomized, single-blinded, placebo-controlled study was to do a systematic examination of the effects of different antidopaminergic mechanisms on prolactin secretion in healthy volunteers. A 7-day intervention was performed with aripiprazole, haloperidol, or reserpine. Prolactin levels changed significantly in the haloperidol (from 177.2 ± 74.6 to 350.7 ± 202.6 mU/L; P < 0.0001) and in the reserpine groups (from 149.6 ± 80.2 to 540.3 ± 280.8 mU/L; P < 0.0001) but not after aripiprazole (from 160.9 ± 65.0 to 189.6 ± 209.6 mU/L; P = 0.69) or placebo (from 211.6 ± 113.4 mU/L to 196.1 ± 85.6 mU/L; P = 0.8). After haloperidol and reserpine, increases in prolactin were significantly more pronounced in women than in men. Furthermore, in women using hormonal contraception, the increase in prolactin was significantly greater than in those without additional estrogen supply. These results demonstrate that the effect of antipsychotic drugs on prolactin levels strongly depends on their mechanism of action. Reserpine, a vesicular monoamine transporter type 2 blocker, causes the most distinct increase. This implies that D? receptor blockade on the lactotrophs is not the sole major cause leading to hyperprolactinemia. The partial agonistic effect of aripiprazole was sufficient to maintain prolactin on physiologic levels. The strong influences of sex and hormonal contraception underline the sensitizing effect of estrogens to the antipsychotic-induced prolactin increase.