A device to evaluate motor and autonomic impairment

Various devices have been developed to assess impairment of the autonomic nervous system, while other devices have been developed to evaluate the motor system. However, no devices have been developed to examine the interaction between the autonomic and somatic nervous systems. Therefore, the device described here, a square platform which was 0.7 × 0.7 m in length and 0.1 m thick, was developed to examine somatic-autonomic interaction. The device can be used by placing it directly on the floor or on 1 of 2 pivots; one that allowed the platform to move 0.2 m (±44.1°) in the front to back or side to side direction and one that allowed both movements together. Strain gauge load cells in the platform measured sway and tremor during the subjects attempt to balance and a continuous blood pressure monitor and the ECG were used to assess the response of the autonomic nervous system (heart rate variability). The device was tested on 5 normal subjects and the following was evaluated: (1) sway during standing, (2) weight shift during standing, (3) frequency of sway and extent of sway during standing, (4) sympathetic and parasympathetic alterations in the ANS during attempted balance, and (5) phase delays between motor and autonomic responses. The results showed that, with increasing balance challenge, sway increased, tremor increased, the sway angle increased and sway was positively correlated with heart rate and negatively correlated with blood pressure. A balance challenge significantly increased sympathetic activity but not parasympathetic activity. This device should have useful applications in assessing motor impairments and sensory and autonomic impairments in a variety of conditions.     

Association of cardiac autonomic neuropathy with alteration of sympatho-vagal balance through heart rate variability analysis

Early sub-clinical assessment of severity of cardiac autonomic neuropathy (CAN) and intervention are of prime importance for risk stratification and early treatment in preventing sudden death due to silent myocardial infarction. The Ewing battery is currently the diagnostic tool of choice but is unable to detect sub-clinical disease and requires patient cooperation. Time and frequency domain analysis have several shortcomings including sensitivity to recording length, respiratory activity and non-stationarities in the ECG signal. An important step forward is to have a non-invasive method of detecting CAN that is robust against these shortcomings and has a higher sensitivity for the presence of both sub-clinical and overt clinical disease. This study presents a novel parameter, tone–entropy (T–E) that analyses heart rate variability (HRV) of 20 min lead II ECG recordings. Tone (T) represents sympatho-vagal balance and entropy (E) the autonomic regularity activity. Thirteen normal subjects without (CAN?) and 21 with CAN (CAN+) participated in this study. Among 21 CAN+ subjects, 13 are early CAN+ (eCAN+), eight are definite CAN+ (dCAN+) according to autonomic nervous system function tests as described by Ewing. The results showed that tone was higher and the entropy was lower in the dCAN+ group (T = ?0.033 to ?0.010 and E = 1.73–2.24) compared with the eCAN+ (T = ?0.0927 to ?0.0311 and E = 2.0–2.65) and normal (T = ?0.128 to ?0.0635 and E = 2.64–3.15) group. The research verified that T–E is a suitable method to determine the presence of CAN that correctly identifies experimentally induced changes in cardiac function akin to parasympathetic and sympathetic dysfunction and differentiates between stages in CAN disease progression identified using the Ewing battery.     

Cardiac autonomic nerve abnormalities in chronic heart failure are associated with presynaptic vagal nerve degeneration

Background: Understanding of the functional and structural disturbances of cardiac autonomic nerves in ventricular hypertrophy and eventual chronic heart failure (CHF) remains unclear. Methods and results: ECG signals were obtained by a radio transmitter from male Wistar rats that received monocrotaline (MCT) via subcutaneous injection. Heart rate (HR) and HR variability (HRV) were analyzed. The RR interval, total power (TP), low frequency (LF) power, high frequency (HF) power, and LF/HF (L/H) power ratio were measured. Ultrastructural changes in cardiac autonomic nerves at the sinoatrial (SA) node region were studied using an electron microscope. TP and HF powers in MCT-induced right ventricular hypertrophy (RVH) and eventual CHF were significantly decreased, and HR was significantly increased at week 5 or later after the MCT injection. The electron microscopic findings indicated the depletion of neurotransmitter vesicles and degradation of parasympathetic but not sympathetic nerve endings in the SA node region of the heart. Conclusion: MCT-induced RVH and CHF rats showed presynaptic vagal nerve degradation prior to sympathetic nerve derangement in the heart.     

Analysis of heart rate variability and skin blood flow oscillations under deep controlled breathing

The effect of deep breathing controlled in both rate (0.25, 0.16, 0.1, 0.07, 0.05 and 0.03 Hz) and amplitude on the heart rate variability (HRV) and respiration-dependent oscillations of forearm/finger skin blood flow (SBF) has been studied in 29 young healthy volunteers. The influence of sympathovagal balance on the respiratory sinus arrhythmia (RSA) amplitude and respiratory SBF oscillations has been studied. The subjects with predominant parasympathetic tonus had statistically significant higher RSA amplitudes in the breathing rate region of 0.03–0.07 Hz than the subjects with predominant sympathetic tonus. In the finger-cushion zone, having a well-developed sympathetic vascular innervations, the amplitudes of respiratory SBF oscillations at breathing rates 0.05 and 0.07 Hz were higher in the group of subjects with predominant parasympathetic tonus. In the forearm skin, where the density of sympathetic innervations is low comparatively to that in the finger skin, no statistically significant differences in the amplitude of respiratory SBF oscillations were found concerning the two groups of subjects.     

Sympathetic and parasympathetic responses to a core disgust video clip as a function of disgust propensity and disgust sensitivity

It is generally assumed that disgust is accompanied by increased activation of the parasympathetic nervous system (PNS). However, empirical support for the role of PNS in disgust is scarce. This study tested whether (i) activation of the PNS is indeed involved in disgust and (ii) disgust-induced autonomic activation is especially pronounced in individuals with high disgust propensity or enhanced disgust sensitivity. Participants (N = 60) viewed a 5 min disgust-inducing video clip. Participants showed increased parasympathetic activity of both the cardiac and the digestive components of the autonomic nervous system (ANS), together with increased sympathetic activation of the cardiac system. ANS responses were independent of subjective disgust and individuals’ habitual disgust propensity or sensitivity. Results support the hypothesis that PNS activation is involved in disgust. The absence of a relationship between subjective and physiological indices of disgust indicates that both types of responses reflect independent phenomena.     

Alteration in biochemical parameters during plateletpheresis in healthy donors: A compendious analysis

ObjectivesDuring plateletpheresis, citrate induces hypocalcemia and hypomagnesemia, which are usually transient and self-limiting, but they can lead to significant donor discomfort. The aim of study was to determine the effect of citrate infusion on a multitude of biochemical parameters during plateletpheresis in healthy donors and to correlate changes with adverse donor reactions.MethodsThe study was conducted on 60 healthy plateletpheresis donors. Blood samples were drawn on three occasions, a baseline pre-donation sample, 30 min at start of procedure and 30 min post procedure. Heparinized samples were taken to measure ionized calcium and plain samples to measure serum calcium, serum magnesium, parathyroid hormone, total protein and serum albumin.ResultsThere was statistically significant decline in mean total calcium (9.27 ± 0.66 mg/dl to 8.72 ± 0.87 mg/dl) and ionized calcium (3.8 ± 0.51 mg/dl to 2.9 ± 0.67 mg/dl) from baseline until 30 min after the start of procedure respectively. A significant fall in serum magnesium, total protein and serum albumin was observed. The mean parathyroid hormone showed significant increase from baseline levels till at the completion of procedure (19.94 ± 12.1 pg/ml to 92.08 ± 36.78 pg/ml). If the yield was set constant, there was negative correlation between ACD used and pre-donation platelet count. Majority of adverse donor reactions were hypocalcemic reactions, which were more with Amicus double yield plateletpheresis and were managed with calcium supplementation.ConclusionPlateletpheresis induces marked reduction in serum calcium and magnesium levels. Moreover, increase in parathyroid hormone levels was significant. In addition, decline in total protein and serum albumin may be a concern in donors also participating in plasmapheresis.     

Linear and non-linear analysis of heart rate variability in master athletes and healthy middle-aged non-athletes

The present study examined the autonomic cardiac modulation of veteran athletes by the use of traditional and modern methods of heart rate variability (HRV) analysis. Twenty-nine healthy male master soccer players were divided into two groups; group A consisted of fourteen participants (age 48.9 ± 5.8 years), who were engaged to regular aerobic exercise and group B of fifteen sedentary ones (age 50.8 ± 5.7 years). Sixteen age-matched non-athletes formed control group C. All participants underwent ambulatory 24-h continuous electrocardiogram monitoring for the calculation of time and frequency domain HRV indices. Additionally, Poincaré analysis SD₁ and SD₂ as well as multiresolution wavelet analysis σ_wav(16) and σ_wav(32) markers were calculated. Time-domain indices were significantly increased in group A compared to groups B and C. Group A presented greater values of SD₁ (by 43%, p < 0.01 and 34.4%, p < 0.05 than groups B and C respectively) and SD₂ (by 26% compared to B and by 34.1% to C, p < 0.05). Index σ_wav(16) was higher in group A than in B and C by 35.6% (p < 0.01) and 23.5% (p < 0.05) respectively and so did σ_wav(32) by 22% (p < 0.05) and 24% (p < 0.05). Strong correlations were reported among indices. In conclusion, physically active master athletes attain better cardiac autonomic activity than sedentary counterparts, as proved by the application of Poincaré and multiresolution wavelet analyses, which can be useful research tools of cardiac autonomic modulation in sports cardiology.     

Nutrition education in postmenopausal women: Changes in dietary and cardiovascular indices

ObjectiveThe aim of the current study was to examine whether a diet rich in dairy products followed by a nutrition education program for the prevention of osteoporosis could have any adverse effect on certain cardiovascular disease (CVD) risk factors over a 5-month intervention period.MethodsA total sample of 82 women (55–65 years old) was randomized to a dietary intervention group (IG: n = 42), attending biweekly nutrition education program and provided with low-fat, fortified dairy products and to a control group (CG: n = 40). Changes in dietary, biochemical and clinical indices related to CVD were determined at the end of the 5-month intervention period.ResultsThe IG was found to have a higher decrease in the percentage of energy intake derived from total fat and a higher increase in the intake of calcium, phosphorus, magnesium and potassium compared to the CG (p < 0.05). Furthermore, the IG subjects were found to have a lower increase in BMI (0.7 ± 0.1 versus 1.4 ± 0.2 Kg/m², p = 0.011) and systolic blood pressure (SBP) (2.5 ± 2.9 versus 7.8 ± 2.2 mmHg, p = 0.040) and a higher decrease in serum total cholesterol (−5.2 ± 3.3 versus 6.9 ± 5.1 mg/dl, p = 0.042) and LDL-cholesterol levels (−20.0 ± 2.6 versus −12.4 ± 4.2 mg/dl, p = 0.034) compared to the CG.ConclusionsThe findings of the current study indicate that a dietary intervention aiming to minimize the risk for osteoporosis did not have any adverse effects on CVD risk factors. On the contrary, it has induced favourable changes in BMI, serum lipids and SBP.     

Utility of serum IgG,IgG4 and carbonic anhydrase II antibodies in distinguishing autoimmune pancreatitis from pancreatic cancer and chronic pancreatitis

PurposeAutoimmune pancreatitis (AIP) can mimic pancreatic cancer in its clinical presentation, imaging features and laboratory parameters. The aim of our study was to compare IgG, IgG4 and anti-CAIIAb serum levels in patients with AIP, pancreatic adenocarcinoma (PA) and chronic pancreatitis (CP) and to assess their clinical significance and utility in differential diagnosis of pancreatic diseases.Patient/methodsThe study included 124 patients: 45 with PA, 24 with AIP and 55 with CP. Peripheral venous blood samples were obtained from all analyzed patients at the time of hospital admission and total IgG, IgG4 and anti-CAIIAB serum levels were measured using ELISA tests.ResultsSerum levels of IgG, IgG4 and anti-CAIIAb were significantly higher in patients with AIP compared to PA and CP patients (p < 0.001). In AIP patients the median IgG levels were 19.7 g/l, IgG4 levels – 301.9 mg/dl and anti-CAIIAb – 81.82 ng/ml, compared to 10.61 g/l, 123.2 mg/dl and 28.6 ng/ml, respectively, in PA patients. IgG4 for the cut-off 210 mg/dl showed the best sensitivity and specificity (83.8% and 89.5%) in AIP diagnosis compared to IgG (69.3% and 87.3%, respectively) and anti-CAIIAb (45.3% and 74.3%). However, 16 (35.5%) patients with PA and 14 (25.4%) patients with CP had IgG4 levels greater than 140 mg/dl. Moreover, in 3 (6.67%) patients with pancreatic cancer those values were greater than 280 mg/dl. No patients with CP had IgG4 more than 280 mg/dl.ConclusionsIgG4 at cut-off 210 mg/dl showed the best sensitivity and specificity in AIP diagnosis compared to IgG and anti-CAIIAb, however elevations of serum IgG4 may be seen in subjects without AIP, including pancreatic cancer.     

Protective effects of epigallocatechin gallate (EGCG) on streptozotocin-induced diabetic nephropathy in mice

There is increasing evidence suggesting that antioxidants in green tea extracts may protect kidneys on the progression of end-stage renal disease. We investigated the protective impacts of (−)-epigallocatechin 3-O-gallate (EGCG) against streptozotocin (STZ)-induced diabetic nephropathy in mice. The mice were divided into 5 groups (n = 10 per group): control (saline, i.p.), STZ (200 mg/kg, i.p.), EGCG50 (50 mg/kg, S.Q.), EGCG100 (100 mg/kg, S.Q.), and EGCG200 (200 mg/kg, S.Q.). Animals were sacrificed at scheduled times after EGCG administration and then quantitative and qualitative analysis were performed. Compared with the control group, the STZ group showed an increase in levels of blood glucose, blood urea nitrogen, creatinine and urine protein amounts with a decrease in body weight. All the above parameters were significantly reversed with EGCG treatment, especially in the EGCG100 group. After STZ injection, there was a mesangial proliferation with increased renal osteopontin accumulation and its protein expression in the glomeruli and the proximal tubules. Mice kidneys after EGCG-treatment showed a reduced expression of above parameters and relatively improved histopathological findings. These results indicated that EGCG 100 mg/kg might provide an effective protection against STZ-induced diabetic nephropathy in mice by osteopontin suppression.     

Measurement fidelity of heart rate variability signal processing: The devil is in the details

Heart rate variability (HRV) is a particularly valuable quantitative marker of the flexibility and balance of the autonomic nervous system. Significant advances in software programs to automatically derive HRV have led to its extensive use in psychophysiological research. However, there is a lack of systematic comparisons across software programs used to derive HRV indices. Further, researchers report meager details on important signal processing decisions making synthesis across studies challenging. The aim of the present study was to evaluate the measurement fidelity of time- and frequency-domain HRV indices derived from three predominant signal processing software programs commonly used in clinical and research settings. Triplicate ECG recordings were derived from 20 participants using identical data acquisition hardware. Among the time-domain indices, there was strong to excellent correspondence (ICC_avg = 0.93) for SDNN, SDANN, SDNNi, rMSSD, and pNN50. The frequency-domain indices yielded excellent correspondence (ICC_avg = 0.91) for LF, HF, and LF/HF ratio, except for VLF which exhibited poor correspondence (ICC_avg = 0.19). Stringent user-decisions and technical specifications for nuanced HRV processing details are essential to ensure measurement fidelity across signal processing software programs.     

Elastic modulus and collagen organization of the rabbit cornea: Epithelium to endothelium

The rabbit is commonly used to evaluate new corneal prosthetics and study corneal wound healing. Knowledge of the stiffness of the rabbit cornea would better inform the design and fabrication of keratoprosthetics and substrates with relevant mechanical properties for in vitro investigations of corneal cellular behavior. This study determined the elastic modulus of the rabbit corneal epithelium, anterior basement membrane (ABM), anterior and posterior stroma, Descemet’s membrane (DM) and endothelium using atomic force microscopy (AFM). In addition, three-dimensional collagen fiber organization of the rabbit cornea was determined using nonlinear optical high-resolution macroscopy. The elastic modulus as determined by AFM for each corneal layer was: epithelium, 0.57 ± 0.29 kPa (mean ± SD); ABM, 4.5 ± 1.2 kPa, anterior stroma, 1.1 ± 0.6 kPa; posterior stroma, 0.38 ± 0.22 kPa; DM, 11.7 ± 7.4 kPa; and endothelium, 4.1 ± 1.7 kPa. The biophysical properties, including the elastic modulus, are unique for each layer of the rabbit cornea and are dramatically softer in comparison to the corresponding regions of the human cornea. Collagen fiber organization is also dramatically different between the two species, with markedly less intertwining observed in the rabbit vs. human cornea. Given that the substratum stiffness considerably alters the corneal cell behavior, keratoprosthetics that incorporate mechanical properties simulating the native human cornea may not elicit optimal cellular performance in rabbit corneas that have dramatically different elastic moduli. These data should allow for the design of substrates that better mimic the biomechanical properties of the corneal cellular environment.     

Retentissement du tabagisme maternel sur le comportement du nouveau-né : dosage des métabolites urinaires de la nicotine chez la mère et le nouveau-né

Influence of maternal smoking on newborn's behaviour: determination urinary nicotine metabolites levels in mothers and infants.Objective. – Effects of smoking during pregnancy on newborn's behaviour at 2 or 3 days. Intoxication? Withdrawal?Population and method. – Urinary cotinine levels were measured using DPC^® technique in 142 mothers during labour and in their 138 normal, full-term newborns kept with their mothers at about 3 days. Infants' Finnegan scores were estimated, Lamour/Barraco tests, too.Results. – There are significant correlations: maternal cotinine (ng/mg) = 382,67 + 264,79 cigarettes/day, R = 0,70, P < 0,001; newborn cotinine (ng/mg) = 74,28 + 68,49 cigarettes/day, R = 0,69, P < 0,001; newborn cotinine (ng/mg) = 57,59 + 0,18 maternal cotinine (ng/mg), R = 0,73, P < 0,001. Newborns' cotinine concentrations (47% corresponds with smokers' levels) are with breast-milk 4,94 times lower than that of their mothers vs 3,65 with artificial milk. Incidence of colic increases (P = 0,008) and the neurologic scores average decreases (P = 0,059).Conclusions. – Newborns' high cotinine levels, digestive and neurologic symptoms modification suggest tobacco intoxication. Therefore withdrawal would appear later. Breast-milk seems to accelerate cotinine elimination.     

l-Arginine supplementation enhances eNOS expression in experimental model of hypercholesterolemic rabbits aorta

Introduction: Diminished bioavailability of nitric oxide is crucial in endothelial dysfunction and the development of atherosclerosis. Several studies have found that l-arginine as a nitric oxide (NO) donor has beneficial effect in prevention of atherosclerosis, but the mechanism is not completely known. We hypothesized that increased endothelial nitric oxide synthase (eNOS) and/or decreased inducible NOS (iNOS) expressions might be involved in the preventive effects of l-arginine in hypercholesterolemic rabbits. Methods: Seventeen male rabbits were divided randomly in two groups. They received rabbits chow supplemented with 1% cholesterol (group 1, n = 8) and the other group received also l-arginine (3% in drinking water) (group 2, n = 9) for 1 month. Blood samples were obtained before and after the experiment. At the end of experiment, the aortas were harvested. The serum levels of cholesterol and low-density lipoproteins (LDL) were measured. The intima/media thickness (IMT) ratio was measured and the determination of fatty streak formation was done with the aid of light microscopy. eNOS and iNOS expression in aorta were studied with immuohistochemistery. Results: The IMT ratio in first group having fatty streaks was 0.287 ± 0.15. No fatty streak lesion was detected in l-arginine-treated group. The results also indicated that eNOS expression (intensity) in aortas was significantly higher in l-arginine-treated group (group 1: 13.62 ± 2.7 and group 2: 21.77 ± 2.8; p < 0.05), but no significant difference was observed for iNOS expression between the groups. Conclusion: The expression of eNOS plays an important role in the protection of the vessel wall from atherosclerosis. l-Arginine in drinking water has a beneficial effect in the enhancement of eNOS protein expression.     

Vasopressin and sympathetic systems mediate the cardiovascular effects of the GABAergic system in the bed nucleus of the stria terminalis

The bed nucleus of the stria terminalis (BST) is an important part of the limbic system. It has been shown that chemical stimulation of the BST elicited cardiovascular depressive and bradycardic responses. It was also demonstrated that GABA is present in the BST, though its role in cardiovascular control is not yet understood. This study was performed to find the effects of GABA receptor subtypes in the BST on cardiovascular responses and to find the possible mechanisms that mediate these responses in urethane-anesthetized rats. Microinjection of muscimol (500 pmol/100 nl), a GABA_A agonist, into the BST produced a weak unsignificant decrease in the mean arterial pressure (MAP) and heart rate (HR). Injection of bicuculline methiodide (BMI, 100 pmol/100 nl), a GABA_A antagonist, caused a significant increase in the MAP (41.3 ± 5.1 mmHg) as well as in the HR (33.2 ± 5.6 beats/min). Injection of two doses (500 and 1000 pmol/100 nl) of phaclofen, a GABA_B antagonist, produced no significant change in either MAP or HR. Administration (i.v.) of the muscarinic receptor blocker, homatropine methyl bromide had no effect on the magnitude of mean arterial pressure or heart rate responses to BMI. This suggests that the parasympathetic system is not involved in these responses. However, administration (i.v.) of the nicotinic receptor blocker, hexamethonium bromide had no effect on the magnitude of mean arterial pressure response but abolished heart rate response to BMI. This suggests that the sympathetic system is involved in the bradycardic effect of GABA. On the other hand, administration (i.v.) of a selective vasopressin V₁ receptor antagonist abolished the pressor effect of BMI, which indicates that the GABAergic system of the BST decreases the arterial pressure via tonic inhibition of vasopressin release. In summary, we demonstrated, for the first time, that GABA exerts its influence in the BST through the activation of GABA_A, but not GABA_B, receptors that, in turn, tonically inhibit vasopressin release and sympathetic outflow to the heart.     

Fine structural survey of tyrosine hydroxylase immunoreactive terminals in the myenteric ganglion of the rat duodenum

We have examined whether the noradrenergic neurons have direct synaptic projections to the myenteric ganglion neurons of the duodenum and the ultrastructure of their terminals by using immunogold–silver labeling for tyrosine hydroxylase. In the neuropil of the myenteric ganglia, about half of the axon terminals contained round clear vesicles and the rest of them contained pleomorphic clear vesicles. The sizes of axon terminals contacting the dendrites as a whole were 1.62 ± 0.07 μm. All axon terminals formed asymmetric synaptic contacts with dendrites or somata. Immunohistochemical study revealed that the tyrosine hydroxylase-immunoreactive nerve terminals were distributed throughout the ganglia and contained exclusively pleomorphic clear synaptic vesicles (about 20–80 nm long). The tyrosine hydroxylase-immunoreactive terminals were generally large (1.99 ± 0.07 μm). A considerable number of the tyrosine hydroxylase-immunoreactive terminals made asymmetric synaptic contacts with small dendrites, spines or somata of the myenteric ganglion neurons. Serial ultrathin sections through the myenteric neurons revealed that about 16% of the total number of axosomatic terminals showed tyrosine hydroxylase immunoreactivity. These results indicated that the myenteric ganglion neurons of the duodenum receive direct synaptic projection of sympathetic noradrenergic neurons and that their terminals contain pleomorphic vesicles and form asymmetric synaptic contacts.     

Sonographic evaluation of endothelial function in letrozole and tamoxifen users

ObjectivesStudies have shown that women previously treated for breast cancer present fewer cardiovascular events, indicating a possible protective effect of tamoxifen treatment. The effects of these aromatase inhibitors on cardiovascular protection remain controversial. The aim of this study was to compare some cardiovascular risk markers among breast cancer survivors following treatment with tamoxifen group (TMXg), letrozole group (LTZg) or no endocrine treatment group (NETg).MethodsA total of 103 breast cancer survivors: 35 using TMXg, 34 using letrozole group (LTZg) and 34 using no endocrine treatment group (NETg) were evaluated. Ultrasonographic evaluation of brachial artery flow-mediated dilation (FMD), carotid intima–media thickness (IMT) and stiffness index (β); blood total cholesterol, HDL and triglycerides were assessed.ResultsAll three groups presented similar values of HDL and IMT. TMXg showed the lowest total cholesterol (219.29 ± 36.31 mg/dL vs. 250.59 ± 38.37 mg/dL vs. 245.09 ± 35.35 mg/dL; TMXg vs. LTZg vs. NETg, respectively; p < 0.01—ANOVA), the highest triglycerides (139.34 ± 41.82 mg/dL vs. 111.35 ± 28.22 mg/dL vs. 122.09 ± 33.42 mg/dL; p < 0.01), the highest FMD (6.32 ± 2.33% vs. 4.10 ± 2.06% vs. 4.66 ± 2.52%; p < 0.01) and the lowest stiffness index (β) (5.08 ± 1.68 vs. 6.28 ± 1.75 vs. 5.99 ± 1.86; p = 0.01). LTZg did not differ significantly from NETg on any evaluated parameter.ConclusionsWe did not observe any effect of LTZg on the evaluated cardiovascular risk parameters compared to NETg. As such, the observed difference on lipid values, stiffness index (β) and FMD between women receiving tamoxifen and letrozole might be best attributed to the beneficial effect of tamoxifen than to a detrimental effect of letrozole.     

Assessment of acute toxicity and histopathology of the fungicide captan in rainbow trout

Acute toxicity of the fungicide, captan, to juvenile rainbow trout was evaluated under static-renewal test condition. Actual concentrations of captan ranged from 0.05 to 1.00 mg/L. The concentrations of captan that killed 50% of the rainbow trout (3.11 ± 0.8 g) within 24 (24 h; LC₅₀), 48, 72 and 96 h were 0.57 ± 0.09, 0.49 ± 0.10, 0.44 ± 0.11 and 0.38 ± 0.13 mg/L (95% confidence limits), respectively. None of the unexposed control fish died and the first fish died 6 h after exposure to captan (≥0.65 mg/L). Hypertrophy, separation of epithelium from lamellae, lamellar fusion, and epithelial cell necrosis were observed on captan exposed fish. Gills also had scattered areas of focal lamellar hyperplasia. Fish exposed to fungicide had inflammation and necrosis in liver, trunk kidney and spleen. In order, the most affected organs were gill, trunk kidney and liver.     

Diabetes mellitus affects activity of calcium/calmodulin-dependent protein kinase II alpha in rat trigeminal ganglia

The activity of calcium/calmodulin-dependent protein kinase II alpha (CaMKIIα) may play a critical role in the modulation of nociceptor activity and plasticity of primary sensory trigeminal neurons. The aim of this study was to investigate the immunoreactivity of phosphorylated CaMKIIα (pCaMKIIα) in subpopulations of trigeminal ganglion (TG) neurons in rat models of early diabetes type 1 (dm1) and 2 (dm2). DM1 model was induced with intraperitoneally (i.p.) injected streptozotocin (STZ) (55 mg/kg). DM2 rats were fed with the high fat diet (HFD) for 2 weeks and then received 35 mg/kg of STZ i.p. Two weeks and 2 months after the STZ-diabetes induction, rats were sacrificed and immunohistochemical analysis for detection of pCaMKIIα immunoreactivity and double immunofluorescence labelling with isolectin (IB4) was performed. Increased intensity of pCaMKIIα immunofluorescence, restricted to IB4-negative small-diameter neurons, was seen in TG neurons two months after STZ-DM1 induction. DM1 model, as well as the obesity (control dm2 groups) resulted in neuronal impaired growth while dm2 model led to neuron hypertrophy in TG. Observed changes may play a critical role in the modulation of nociceptor activity and plasticity of primary sensory trigeminal neurons. In future, innovative strategies for modulation of CaMKIIα activity in specific subpopulations of neurons could be a novel approach in therapy of diabetic trigeminal neuropathy.