Pre-and postnatal exposition to fluorides induce changes in rats liver morphology by impairment of antioxidant defense mechanisms and COX induction.

INTRODUCTION: Fluorides are common in the environment and are absorbed mostly in the stomach and gut, it can easily move through cell membranes and its accumulation can cause harmful effects in skeletal and soft tissues. One of the most important F- accumulation sites is the liver. The aim of this study was to determine whether F- can cause inflammation in rat liver by affecting the activity of antioxidant enzymes and changes in the synthesis of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2). MATERIALS AND METHODS: An in vivo model of prenatal and postnatal exposure to sodium fluoride (NaF) was used to carry out the experiment. Animals from control group received tap water to drink, while animals exposed to F- received drinking water containing NaF, 50 mg/L. In serum and liver we analyzed F- concentration, in liver - antioxidant enzymes activity, PGE2 and TXB2 concentration and immunolocalization of COX1 and COX2 proteins were measured. RESULTS: We observed significant changes in F- concentration only in liver. The results of this study showed that F- affects antioxidant enzymes activity, COX2 protein expression and PGE2 synthesis in liver. Also, in some regions of the liver of rats exposed to F-, the hepatocytes were diffusely altered, with changes resembling microvesicular steatosis. CONCLUSION: Chronic exposure to F- during development causes an accumulation of this element in the liver and changes in antioxidant enzymes activity and cyclooxygenase expression. Long term exposure to this element is toxic to the liver and can cause disturbances in its homeostasis.

The short chain fatty acids and lipopolysaccharides status in Sprague-Dawley rats fed with high-fat and high-cholesterol diet.

Short chain fatty acids (SCFA) are produced by the gut microbiota during the fermentation of non-digestible polysaccharides. Diet is a major factor driving the composition and metabolism of the colonic microbiota. The aim of our study was to examine how a fat-rich and cholesterol-rich diet that, which leads to many metabolic disorders, affects the SCFA profile and lipopolysaccharide (LPS) concentration. The experiment was carried out on 72 male, 8-weeks-old Sprague-Dawley rats. The study group (n = 30 rats) received high-fat and high cholesterol diet (HFHCh). The control group (n = 30) received standard food for laboratory rats. The rats from study and control groups were sacrificed after 4, 8, 12, 16 and 20 weeks after start of dietary exposure. The analysis of SFA in feces was performed using gas chromatography (Agilent Technologies 1260 A GC). The exposure to high-fat and high-cholesterol diet was associated with significant changes in SCFA levels. Relative to the control, each of HFHCh subgroup revealed a statistically significant decrease in butyrate (12.5% ± 5.7% versus 32.8% ± 9.1%) and an increase in propionate level (45.4% ± 6.2% versus 19.14% ± 7.1%). The ratio of acetate: propionate: butyrate was also changed (from 1.1: 0.6: 1 for control groups to 3 : 3,6 : 1 for HFHCh groups). The main SCFA in the HFHCh group was propionate instead of acetate. The dietary exposure resulted in significant differences in LPS concentration. After 12 weeks of HFD exposure, LPS concentration was significantly higher compared to control groups (P < 0.05). Our study showed that HFHCh diet affected butyrate and propionate production associated with an increase in LPS secretion. The hypothesis that observed changes could result in intestinal imbalance secondary to gut barrier dysfunction requires further studies.

The effect of low levels of lead (Pb) in the blood on levels of sphingosine-1-phosphate (S1P) and expression of S1P receptor 1 in the brain of the rat in the perinatal period.

Sphingolipids are the main components of the lipid membrane. They also perform structural functions and participate in many signal transmission processes. One of the bioactive sphingolipids is sphingosine-1-phosphate (S1P), a ligand for five G protein-coupled receptors (S1PRs1-5), which can also act as an intracellular second messenger. S1P is responsible for the stimulation of progenitor cells in the brain, but it can also induce apoptosis of mature neurons. This study is aimed at assessing the effect of pre- and neonatal exposure to permissible Pb concentrations on S1P levels and S1PR1 (EDG1) expression in the prefrontal cortex, cerebellum, and hippocampus of rats. The concentrations of S1P were determined by RP-HPLC, S1PR1 expression was determined by RT PCR and Western Blot, and receptor immunolocalization was determined by immunohistochemistry method. Our results showed that even low blood Pb concentrations, i.e. within the acceptable limit of 10 µg/dL caused changes in the concentration of S1P in the cerebellum, prefrontal cortex, and hippocampus. Our data also showed a significant decrease in the level of S1PR1 in all studied part of brain, without significant changes in S1PR1 gene expression. Pre- and neonatal exposure to Pb also resulted in a decrease in the expression of S1PR1 in glial cells in all regions of the Cornu Ammonis (CA1-CA4) and Dentate Gyrus in the hippocampus, as well as in all layers of the cerebellum and prefrontal cortex, compared to the unexposed control group.

The Influence of Fluorine on the Disturbances of Homeostasis in the Central Nervous System.

Fluorides occur naturally in the environment, the daily exposure of human organism to fluorine mainly depends on the intake of this element with drinking water and it is connected with the geographical region. In some countries, we can observe the endemic fluorosis-the damage of hard and soft tissues caused by the excessive intake of fluorine. Recent studies showed that fluorine is toxic to the central nervous system (CNS). There are several known mechanisms which lead to structural brain damage caused by the excessive intake of fluorine. This element is able to cross the blood-brain barrier, and it accumulates in neurons affecting cytological changes, cell activity and ion transport (e.g. chlorine transport). Additionally, fluorine changes the concentration of non-enzymatic advanced glycation end products (AGEs), the metabolism of neurotransmitters (influencing mainly glutamatergic neurotransmission) and the energy metabolism of neurons by the impaired glucose transporter-GLUT1. It can also change activity and lead to dysfunction of important proteins which are part of the respiratory chain. Fluorine also affects oxidative stress, glial activation and inflammation in the CNS which leads to neurodegeneration. All of those changes lead to abnormal cell differentiation and the activation of apoptosis through the changes in the expression of neural cell adhesion molecules (NCAM), glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF) and MAP kinases. Excessive exposure to this element can cause harmful effects such as permanent damage of all brain structures, impaired learning ability, memory dysfunction and behavioural problems. This paper provides an overview of the fluoride neurotoxicity in juveniles and adults.

Fluoride as a factor initiating and potentiating inflammation in THP1 differentiated monocytes/macrophages.

It is well known that exposure to fluorides lead to an increased ROS production and enhances the inflammatory reactions. Therefore we decided to examine whether cyclooxygenases (particular COX-2) activity and expression may be changed by fluoride in THP1 macrophages and in this way may change the prostanoids biosynthesis. In the present work we demonstrate that fluoride increased concentration of PGE2 and TXA2 in THP1 macrophages. Following exposure to 1-10 µM NaF, COX-2 protein and COX-2 transcript increased markedly. COX-2 protein up-regulation probably is mediated by ROS, produced during fluoride-induced inflammatory reactions. Additional fluoride activates the transcription factor, nuclear factor (NF)-kappaB, which is involved in the up-regulation of COX-2 gene expression. This study indicated that even in small concentrations fluoride changes the amounts and activity of COX-1 and COX-2 enzymes taking part in the initiating and development of inflammatory process.

The spatial substructure of visual receptive fields in the cat's superior colliculus.

Although the direction selective properties of the superficial layer cells of the cat's superior colliculus have been extensively studied, the mechanisms underlying this property remain controversial. With the aim to understand the mechanism(s) underlying directional selectivity of collicular neurons we examined the substructure of their visual receptive fields. 1. The strength of cell responses and the direction selectivity indices varied in relation to the location of the tested region within the receptive field and the amplitude of stimulus movement. 2. Decrease of the amplitude of motion resulted in a decrease of direction selectivity index both in the group of direction-selective cells and in the group of cells classified as direction nonselective but with a directional bias. 3. The decrease of direction selectivity for small amplitude movement resulted mainly from increase in the magnitude of response in the nonpreferred direction of movement. 4. These results suggest that the receptive fields of most collicular cells are composed of subregions with different response profiles and indicate that inhibitory mechanisms dictate direction selectivity of collicular cells.

The physically-challenged athlete: medical issues and assessment.

The rate and pattern of injuries is similar in both physically-challenged and able-bodied athletic participation. However, understanding of the unique medical issues faced by physically-challenged athletes is necessary in conducting appropriate pre-participation evaluations and developing strategies for injury prevention and medical management. Review of the literature provides insight for choosing relevant tests and interpreting components of the physical examination for this population. More research is needed in the management of medical problems specific to the physically-challenged athlete.

Summation effects in receptive fields of the cat's pretectal neurons to stationary and moving visual stimuli.

1. Numerous investigations have shown that the cat's pretectal region (PR) is involved in performance of various visual habits, visually guided behaviour and learning processes. Thus, visually driven PR neurons must have abilities to integrate incoming sensory information. 2. Responses of 102 PR neurons to moving and stationary visual stimuli were investigated in cats. Special attention was paid to the comparative characteristics of summation processes in the same neuron elicited by stationary and moving visual stimuli. 3. The results indicate that only a small proportion (20%) of pretectal neurons revealed similar courses of summation for stationary and moving stimuli. The great majority of neurons (about 80%) showed differentiated courses of summation, depending on the type of visual stimuli used. 4. These data indicate that there are probably discrete mechanisms in the PR which contribute to integration of sensory information in the visually sensitive cells according to the different types of visual stimuli used.

Electrical activity of the acutely isolated pons in cats.

The cat's pons was isolated by two brainstem transections, at the junction of medulla and pons and at the junction of pons and midbrain. In the deafferented pons the EEG activity was virtually absent, whereas the spatial density of active units and the rate of their spontaneous spike activity were at a high level. In the pons of control preparations with brainstem transected only at the ponto-midbrain junction the EEG activity was present, while the single-unit activity was such as in the isolated pons. The electrical activity of the isolated pons was similar to that previously described in the cat's isolated midbrain. The discrepancy between EEG and single-unit activity suggests that in the deafferented pons or midbrain many neurones are asynchronously autoactive. Also, these results show that a flat EEG record is not necessarily a sign of absence of the neural activity and neural death.

Spatial organization of receptive fields of cat's. Hippocampal visually driven neurones.

According to the spatial configurations of receptive fields two broad groups of neurones in dorsal hippocampal region (HR) were distinguished. The receptive field borders of 22 cells have regular (R) smooth contours (squares or rectangles), usually with a horizontally oriented longitudinal axis. The second group was composed of neurones (20 cells) with irregular (IR) configurations of receptive fields. Some neurones (16 cells) of this group had relatively simple spatial configurations of receptive fields and 4 neurones had receptive fields with more intricate spatial configurations which formed complex geometrical shapes in the visual field. The exploration of the distribution of response properties a to stationary flashing spot over the RF surface revealed that the majority of cells with regular receptive fields have heterogeneous stationary structure with ON, ON-OFF and OFF subregions sequentially located in the receptive field, and these neurones, as a rule, were direction-sensitive. The neurones with irregular receptive fields, on the other hand, had a rather homogeneous structure of RFs when tested by a stationary flashing spot and only four neurones of 20 investigated were directionally sensitive.

Common injuries in the child or adolescent athlete.

As more primary care physicians enter the field of Sports Medicine, they will inevitably encounter more injured young athletes than what they may have experienced in their private practices. Recognizing the differences that exist between the young athlete and adult is essential in properly diagnosing and rehabilitating these athletes. As mentioned in our previous article (Caring for the School-Aged Athlete, Primary Care, December 1994), comprehensive care of the young athlete can be quite involved and somewhat different from care of the adult population. This article focuses on some specific injuries unique to younger, skeletally immature athletes, while mentioning the differential diagnosis of some of the other common sports injuries shared by both younger and older athletes.

Caring for the school-aged athlete.

Younger athletes are participating in more activities today than ever before. The primary care physician needs to fulfill the role of guiding these athletes into their activities safely with recommendations to help prevent injuries and other health conditions that may occur during their training and participation. Knowledge covering preparticipation examinations, cardiovascular concerns, nutrition, maturation, and general rehabilitation of injuries will be necessary for the care of these younger athletes. This article provides a general overview of these areas.

Exercise-induced asthma and anaphylaxis.

With increased popularity in exercise, the number of individuals with exercise-induced asthma (EIA), or 'exercise-induced bronchospasm', has increased due to an increased awareness among physicians of the clinical symptoms associated with EIA. EIA affects approximately 75 to 95% of asthmatic patients. 40% of children with allergic rhinitis have EIA, whereas only 3 to 11% of nonasthmatics have EIA. Although athletes with asthma have been recognised for years, EIA in nonasthmatic individuals has gained recognition since the 1984 Olympics. Vague symptoms of recurring poor performance, fatigue despite adequate conditioning, or 'getting winded' during an athlete's usual workout may be the presenting complaints. Athletes may be more likely to attribute these symptoms to poor conditioning or an upper respiratory infection, and not seek immediate assistance. Younger athletes may complain of stomach ache or refuse to participate in strenuous play because of an inability to keep up with other children. Additionally, an awareness of exercise-induced anaphylaxis needs to be considered when discussing aspects of airway compromise following exercise; however, its presentation is more urgent than those with EIA. Although the pathophysiology of EIA is somewhat controversial, the most likely explanation is a combination of heat and water loss leading to mediator release. The different medications that have been used to treat EIA are based on theories regarding the bronchial hyperreactivity of EIA.

The Vannini-Rizzoli orthosis: a unique case of thoracic outlet syndrome.

The Vannini-Rizzoli boot is a stabilizing orthosis that allows selected spinal cord injured patients to stand and ambulate. The body positioning required to maintain stability while using these boots can result in an exaggerated "military position" of the shoulders, as the patient braces his shoulders posteriorly to maintain his center of gravity anterior to the ankle axis. This posture produced thoracic outlet compression in this patient. This case emphasizes the need to be aware of this clinical complex when working with this orthosis and suggests the importance of the patient's functional needs in treatment decisions.

Influence of the intertectal connection upon visual responses in the cat's superior colliculus.

Visual responses of single units in the superficial layers of the superior colliculus were examined in cats with pretrigeminal brainstem transections and lesions in the contralateral superior colliculus. The percentage of direction selective cells was decreased in lesioned as compared to non-lesioned cats. This effect may be a result of the elimination of suppression from the contralateral superior colliculus as well as disturbance of the projections from other structures of the contralateral hemisphere.

Properties of visually driven neurons in cats pretectal region.

Properties of visually driven neurons in the cat pretectal region were studied. A detailed investigation of the receptive field (RF) structure revealed, in the majority of neurons, irregular shapes of RF contours. Dark-sensitive and bright-sensitive zones of a neuronal RF had different spatial locations. The majority of pretectal neurons were movement-sensitive and reacted weakly to stationary flashing spots. Although no clear-cut orientation sensitivity was found in the pretectal neurons, some orientations of motion were, nevertheless, more effective. In some cases a non-directional response could be transformed into a directionally-sensitive one by changing the orientation of motion. Out data confirm earlier observations that the pretectal region is involved in the central processing of visual information.

Barbiturate influence upon organization of lateral geniculate receptive fields in cats.

Under different levels of Nembutal anesthesia the spatiotemporal characteristics of receptive fields of cells in the lateral geniculate nucleus were investigated. All units decreased their maintained activity and bursts of spikes occurred spontaneously after administration of the anesthetic. The excitatory domains of the receptive fields were also changed by shortening of the cell's sustained response and enhancement of the postinhibitory transient responses; the spatial extent of these domains being less affected. A qualitatively new excitatory tertiary” domain appeared in the receptive field surround with a latency of 170-300 ms. These effects together with enhancement of the spatiotemporal extent of inhibitory domains suggest that the suppressive action of barbiturate takes place beyond the retina.

The velocity-response curves of the cat's superior colliculus neurons.

The velocity-response curves of the cat's superior colliculus neurons responding to moving stimuli mere studied quantitatively. They were fitted by logarithmic Gaussian curves described by three parameters: optimal stimulus velocity, amplitude and dispersion of the curve. Since reversal of the stimulus movement direction changed neither optimal stimulus velocity nor dispersion of the velocity tuning curve, then the fourth parameter, directional asymmetry, is postulated to describe fully, in conjunction with three parameters mentioned above, the dependence of the neuron response to velocity and direction on the stimulus motion. All parameters were roughly normally distributed and uncorrelated with each other in the sample of cells investigated. Some implications of our results for the classification of cells, and some arguments for population coding” against single cell trigger feature coding are discussed.

The influence exerted by Nembutal on reactivity of the superior colliculus neurons.

Effects of a Nembutal upon responses of the superior colliculus neurons were analyzed in pretrigeminal cats. Most cells were studied during the spindly barbiturate pattern in the EEG. In this condition collicular neurons lose their spontaneous activity, become sluggish in their reactivity to stimuli moving at high velocity, and less sensitive to direction of movement. After a further increase in the anesthesia down to the isoelectric EEG pattern the responses of neurons were gradually depressed and finally neurons became non-driveable by visual stimulation. A possible mechanism responsible for the reduction of the cells excitability is discussed.

Structure of receptive fields of cat pulvinar neurons sensitive to photic stimulation.

Receptive fields of 262 pulvinar neurons were studied. Receptive fields of 142 of these neurons were studied in detail with the aid of a stationary spot of light, flashing in different parts of the receptive field. Depending on responses to presentation of the stationary stimulus the neurons were divided into six groups. The first group included neurons with on-off responses to photic stimulation (44 of 142), the second group neurons with off responses only (42 of 142). In cells of the third group (19 of 142) an on response only was recorded in all structures of the receptive field tested. Neurons of the fourth group (eight of 412) had a receptive field of similar structure to that of the simple receptive fields of neurons in cortical area 17. The fifth group (10 of 142) included neurons with a receptive field of concentric structure, the sixth (19 of 142) consisted of neurons with receptive fields with multiple discharge centers. The structure of the receptive field of these neurons was mosaic, with an irregular distribution of exciting and "silent" zones. The mean responses latency of the pulvinar neurons was 40-70 msec. Responses of neurons with shorter (20 msec) and longer (130-160 msec) latent periods also were recorded.