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Exertional heatstroke and muscle metabolism: an in vivo 31P-MRS study.

An impairment of muscle energy metabolism has been suggested as a predisposing factor for, as well as a consequence of exertional heatstroke (EHS). Thirteen young men were investigated 6 months after a well-documented EHS using 31Phosphorus Magnetic Resonance Spectroscopy (31P-MRS). The relative concentrations of ATP, phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters (PME), and the intracellular pH (pHi) were determined at rest, during a graded standardized exercise protocol (360 active plantar flexions) and during recovery. Also the leg tissue blood flow was determined by venous occlusion plethysmography during the MRS procedure. Sixteen age-matched healthy male volunteers served as control group. In resting muscle, there were no significant differences between the groups as regards pHi, Pi/PCr, and ATP/PCr+Pi+PME ratios. During steady state exercise conditions, effective power outputs were similar for both groups at each level of exercise: 20, 35, and 50% of maximal voluntary contraction (MVC) of the calf muscle. No significant differences were shown between the two groups in Pi/PCr, pHi, or changes of leg blood flow at each level of exercise. At 50% MVC, Pi/PCr was 0.48 +/- 0.08 vs 0.47 +/- 0.05 (P = 0.96), pHi was 6.94 +/- 0.03 vs 6.99 +/- 0.02, respectively (P = 0.13). Finally, the rate of PCr resynthesis during recovery was not significantly different between the two groups: t1/2 PCr = 0.58 +/- 0.07 vs 0.50 +/- 0.05 min, respectively (P = 0.35). Therefore, no evidence of an impairment of muscle energy metabolism was shown in the EHS group during a standardized submaximal exercise using 31P-MRS performed 6 months after an EHS.

Adenosine Triphosphate↗

A rare cause of exertional dyspnoea and hemoptysis in a 30-year-old female.

A young female patient of 30 years of age previously asymptomatic presented with complaints of exertional dyspnoea and hemoptysis with a normal chest roentgenogram. She was eventually diagnosed to have lymphangioleiomyomatosis, a rare pulmonary disorder. In this patient it occurred without any history of current pregnancy or estrogen consumption, as a sporadic entity.

Adult↗

Exertion-induced heat exhaustion. An often overlooked diagnosis.

Exertion-induced heat exhaustion is a potentially lethal condition. The earliest signs include unsteady gait and confusion. Recording of rectal temperature is essential. Skin colour, blood pressure and heart rate are not reliable diagnostic signs. The mainstays of therapy are rapid rehydration and cooling. Prompt diagnosis and rapid effective therapy will minimise the risk of death.

Adult↗

Exertional rhabdomyolysis in unsupervised exercises in a correctional setting: a case study.

Unsupervised overexercise in the prison population can lead to exertional rhabdomyolysis, a condition that can lead to kidney damage and/or failure. Knowledge deficit of the risk from this activity will be addressed. Signs and symptoms of rhabdomyolysis and its sequelae will be presented along with a case study. Inter-departmental responsibilities in the correctional setting will be considered. The importance of recognizing the signs and symptoms of this condition by nurses in various clinical settings will also be explored.

Exercise↗

Vitamins K2, K3 and K5 exert in vivo antitumor effects on hepatocellular carcinoma by regulating the expression of G1 phase-related cell cycle molecules.

A number of studies have shown that various vitamins K, specifically vitamin K2, possessed antitumor activity on various types of rodent- and human-derived neoplastic cell lines. However, there are only a small number of reports demonstrating in vivo antitumor effects of vitamins K. Furthermore, the mechanism of antitumor effects of vitamins K still remains to be examined. In the present study, we examined the antitumor effects of vitamins K2, K3 and K5 on PLC/PRF/5 human hepatocellular carcinoma (HCC) cells in vivo. Furthermore, to examine the mechanism of antitumor actions of these vitamins K, mRNA expression levels of various G1 phase-related cell cycle molecules were evaluated by using a real-time reverse transcription-polymerase chain reaction (RT-PCR) method. HCC-bearing animals were produced by implanting PLC/PRF/5 cells subcutaneously into athymic nude mice, and drinking water containing vitamin K2, K3 or K5 was given to the animals. Treatments with vitamins K2, K3 and K5 were shown to markedly inhibit the growth of HCC tumors. To examine the mechanism of in vivo antitumor effects of vitamins K, total RNA was extracted from HCC tumors, and the expression of G1 phase-related cell cycle molecules was quantitatively examined. Real-time RT-PCR demonstrated that the expression of the cell cycle-driving molecule, cyclin-dependent kinase 4 (Cdk4), in HCC was significantly reduced by the treatments with vitamin K2, K3 and K5. Conversely, the expression of the cell cycle-suppressing molecules, Cdk inhibitor p16INK4a and retinoblastoma, in HCC was significantly enhanced by the treatments with vitamins K2, K3 and K5. These results indicate that vitamins K2, K3 and K5 exert antitumor effects on HCC by regulating the expression of G1 phase-related cell cycle molecules. These results also indicate that vitamins K2, K3 and K5 may be useful agents for the treatment of patients with HCC.

Alanine Transaminase↗

Comparative in vitro investigation of the forces exerted by eye drops and eye spray.

Topical administration of ophthalmic drugs is predominantly carried out in the form of eye drops. The application of an eye spray represents a feasible alternative to drop instillation with regard to the clinical efficacy. In this study the forces exerted during the application of eye drops and eye spray to a surface were measured in vitro and compared with each other. Whereas the maximal forces that occurred with a falling drop tended to increase with greater application distance, the forces decreased with spraying. From an application distance of 3 cm the eye spray proved to have a more favorable mechanical force effect than the eye drops. In view of the loss of experimental liquid caused by spray application as well as the diameter of the spray cone, a spray distance of from 4 cm to 5 cm can be deemed to be optimal.

Administration, Topical↗

Stargardt-like macular dystrophy protein ELOVL4 exerts a dominant negative effect by recruiting wild-type protein into aggresomes.

PURPOSE: Mutations in the gene Elongation of very long-chain fatty acids-4 (ELOVL4) have been shown to be associated with autosomal dominant Stargardt-like macular dystrophy (STGD3). ELOVL4 is expressed in photoreceptors and encodes a putative transmembrane protein of 314 amino acids with an endoplasmic reticulum (ER) retention signal. A 5 bp deletion in exon 6 of ELOVL4 observed in some STGD3 patients results in the truncation of the protein and loss of the ER retention signal. To understand the disease mechanism underlying STGD3 we studied the intracellular trafficking of the wild-type and a 5 bp deletion mutant of ELOVL4. METHODS: Wild-type and mutant ELOVL4 proteins with the N-terminal GFP/V5 tags were expressed in COS-7 cells. Expression and the intracellular localization of the wild-type and mutant proteins were characterized by immunocytochemistry and western blot analysis using tag- and organelle-specific antibodies. Interaction between the wild-type and mutant proteins was studied by two-dimensional gel electrophoresis and fluorescence resonance energy transfer (FRET) analysis. RESULTS: The mutant ELOVL4 protein exerted a dominant negative effect when the wild-type and 5 bp deletion mutant ELOVL4 proteins were co-expressed in COS-7 cells. Immunocytochemical analysis, two-dimensional gel electrophoresis and FRET revealed that the mutant ELOVL4 interacts with the wild-type protein, forming higher molecular mass complexes that accumulate in aggresomes. CONCLUSIONS: In the presence of mutant ELOVL4 protein, the wild-type protein was recruited into perinuclear cytoplasmic inclusions that resemble aggresomes. The interaction between the wild-type and mutant forms of ELOVL4 and the resultant alteration in the trafficking of the wild-type ELOVL4 protein suggest a mechanism for the pathogenicity observed in patients with autosomal dominant STGD3.

Animals↗

Does GDNF exert its neuroprotective effects on photoreceptors in the rd1 retina through the glial glutamate transporter GLAST?

PURPOSE: We previously demonstrated that exogenous glial cell line-derived neurotrophic factor (GDNF) induces histological and functional protection of photoreceptors in the retinal degeneration (rd1) mouse model. The mechanisms underlying such neuroprotection remain elusive. In parallel to this work, we provided evidence for the occurrence of glutamate-mediated excitotoxic phenomena contributing to rod photoreceptor death in the rd1 retina in the companion paper. In the present study, we investigated whether, as demonstrated in other models, GDNF could exert its neuroprotective effect on photoreceptors through Müller glial cells (MGC) by promoting the expression of the glial L-glutamate/L-aspartate transporter (GLAST), an endogenous neuroprotective mechanism against glutamate-mediated excitotoxicity. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to compare the mRNA expression levels of GDNF receptors between rd1 and wild-type mouse retinas as well as between MGC and mixed retinal cell cultures. Recombinant GDNF was applied to pure MGC cultures, to rd1 retinal organ cultures and injected subretinally into rd1 mouse eyes. GLAST expression following GDNF treatment was measured by RT-PCR, immunoblotting and immunohistochemistry. Free glutamate and glutamine levels were quantified in rd1 retinas after GDNF or control treatment using an amino acid analyzer. RESULTS: mRNA expression studies of GDNF receptors, GFRalpha-1 and Ret, demonstrated that GDNF receptors were not exclusively expressed by the degenerating photoreceptor cells but mainly by MGC. Exogenous GDNF application to MGC cultures, rd1 mouse retinal explants and in vivo rd1 mouse retinas increased the expression of GLAST by 48% in retinal explants (p<0.005) and by 25% in vivo (p<0.0005). GLAST protein expression in MGC was particularly increased around degenerative photoreceptors. Free glutamate and glutamine levels in the rd1 retina were not significantly modified by exogenous GDNF. CONCLUSIONS: Our data suggest that, in the rd1 mouse retina, GDNF neuroprotective effect on photoreceptors can be mediated indirectly through the activation of MGC. We demonstrate that injection of recombinant GDNF enhances the expression of GLAST and more particularly around the degenerating photoreceptors. Since we failed to demonstrate that GDNF decreases free glutamate levels, we could not ascertain whether GDNF promoted photoreceptor-survival via an increase of glutamate uptake and, therefore, a change in glutamate distribution.

Animals↗

Amifostine exerts anti-angiogenic activity and suppresses vascular endothelial growth factor secreted by hemopoietic stem/progenitor cells.

OBJECTIVE: To assess, in vitro, the effect of Amifostine (AMF, WR-2721) on angiogenesis and levels of vascular endothelial growth factor (VEGF) secreted from hemopoietic stem/progenitor cell populations. METHODS: We conducted the study in the research laboratories of the Hashemite University, Jordan between September 2003 and January 2005 where we took samples were from Myelodysplastic syndrome (MDS) patients and healthy donors attending Al-Hussein Cancer Center and We determined the proliferation of human umbilical vein endothelial cells (HUVECs) in cultures supplemented with media conditioned with AMF-treated and AMF-untreated pure hemopoietic cells [CD34+ cells, and erythroid, myeloid and megakaryocytic progenitors]. Furthermore, in the same conditioned media, we evaluated levels of elaborated VEGF by a sensitive enzyme linked immunosorbent assay. RESULTS: Biologically, media conditioned with AMF-treated cells reduced proliferation of HUVECs compared to media conditioned with untreated control cells (p<0.05). In cultures of AMF-untreated cells, elaboration of VEGF was higher (p<0.05) in media conditioned with cells from MDS patients compared to healthy donors. A 30 minutes pre-exposure of cells to AMF (500 mM) suppressed levels of VEGF secreted within 24 hours in 63 of 89 evaluated cultures. The percentage of reduction of VEGF in AMF-sensitive cultures was comparable in cultures of MDS cells (18%, 2-37%; median, range) and normal cells (12%, 2-45%). CONCLUSION: The results showed that AMF exerts an anti-angiogenic activity and suppresses the secretion of VEGF in hemopoietic stem/progenitor cells obtained from both healthy individuals and patients with MDS.

Amifostine↗

Anti-allergic Psidium guajava extracts exert an antitumor effect by inhibition of T regulatory cells and resultant augmentation of Th1 cells.

Th1 polarization is one of the mechanisms underlying the therapeutic effects of herbal medicine. The action of anti-allergic agents from Psidium guajava (P. guajava) on T cell immunity in mice was investigated. The addition of P. guajava extracts blocked IL-10-mediated, in vitro induction of T regulatory (Tr) cells from CD4+ splenocytes of C57BL/6 mice, whereas the extracts exerted only a weak or no effect on the development of Th1 and Th2 cells. Accordingly, Tr cells were not induced from splenocytes of mice administered orally with the extracts. Furthermore, P. guajava extracts shifted the Th1/Th2 balance to a Th1 dominant status by directly attenuating Tr cell activity. In a study of tumor immunity, mice pretreated with the extracts exhibited retarded growth of s.c. inoculated B16 melanoma cells. These findings suggest that P. guajava extracts are efficacious for the prevention of tumor development by depressing Tr cells and subsequently shifting to Th1 cells.

Animals↗

Mature dendritic cells generated from patient-derived peripheral blood monocytes in one-step culture using streptococcal preparation OK-432 exert an enhanced antigen-presenting capacity.

Dendritic cells (DCs) have been shown to be potent in inducing cytotoxic T cell (CTL) response leading to the efficient anti-tumor effect in active immunotherapy. Myeloid DCs are conventionally generated from human peripheral blood monocytes in the presence of interleukin (IL)-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF). Streptococcal preparation OK-432, which is known to be a multiple cytokine inducer, has been extensively studied as to its maturation effects on immature DCs using an in vitro culture system. The purpose of this study was to examine whether it could be possible to generate mature DCs directly from peripheral monocytes using OK-432. We specifically focused on the possibility that recombinant cytokines, which are considered to be essential for in vitro DC generation, could be substituted by OK-432. Human peripheral monocytes, which were obtained from patients with advanced cancer, were cultured with IL-4 and OK-432 for 7 days. Cultured cells were compared with DCs generated in the presence of IL-4 and GM-CSF with or without OK-432 with regard to the surface phenotype as well as the antigen-presenting capacity. As a result, the culture of monocytes in the presence of IL-4 followed by the addition of OK-432 on day 4 (IL-4/OK-DC) induced cells with a fully mature DC phenotype. Functional assays also demonstrated that IL-4/OK-DCs had a strong antigen-presenting capacity determined by their enhanced antigen-specific CTL response and exerted a Th1-type T cell response which is critical for the induction of anti-tumor response. In conclusion, human peripheral blood monocytes cultured in the presence of IL-4 and OK-432 without exogenous GM-CSF demonstrated a fully mature DC phenotype and strong antigen-presenting capacity. This one-step culture protocol allows us to generate fully mature DCs directly from monocytes in 7 days and thus, this protocol can be applicable for DC-based anti-tumor immunotherapy.

Antigen-Presenting Cells↗

Age, insulin, SHBG and sex steroids exert secondary influence on plasma leptin level in women.

AIM: As the link between body fat and leptin is well known, the aim of the study was to seek for secondary regulators of plasma leptin level. PATIENTS: 86 women (mean: age 47.0+/-14.3 years; estradiol 50.0+/-60.6 ng/l; FSH 52.4+/-42.9 IU/l; BMI 26.9+/-5.9) divided into three groups according to their BMI. Group A: 39 normal weight women (mean: age 44.4+/-16.0 years; estradiol 69.6+/-79.8 ng/l; FSH 50.4+/-47.7 IU/l; BMI 22.9+/-1.3). Group B: 27 overweighted women (mean: age 55.0+/-6.4 years; estradiol 25.1+/-17.2 ng/l; FSH 75.6+/-26.3 IU/l; BMI 27.7+/-1.6). Group C: 21 obese women with mean: age 48.7+/-12.2 years; estradiol 36.9+/-44.0 ng/l; FSH 42.3+/-36.6 IU/l and BMI 34.6+/-4.9. METHODS: Standard clinical evaluation and hormone evaluation (LH, FSH, prolactin, estradiol, leptin, insulin-like growth factor-I (IGF-I), human growth hormone (hGH), insulin-like growth factor binding protein-3 (IGFBP-3), insulin, dihydroepiandrosterone sulphate (DHEAS), sex hormone binding globin (SHBG) and testosterone were done in basic condition which levels of were measured by RIA kits. Statistical analysis. Shapiro-Wilk test, Mann-Whitney-Wilcoxon u test, Spearman rank correlation coefficient and stepwise multiple regression: p values of 0.05 or less were considered as significant. RESULTS: Taking all women into account (n=86) the plasma leptin level correlated directly with age (r=0.32; p<0.02), body mass (r=0.60; p<0.001), BMI (r=0.71; p<0.001) as well as inversely with estradiol (r=-0.21; p<0.05), IGF-I (r=-0.24; p<0.05), SHBG (r=-0.34; p<0.01) and DHEAS (r=-0.30; p<0.01). However only in the group B leptin/age relation remained (r=0.40; p<0.05) after the division according to BMI. In the group B the leptin /DHEAS (r=-0.40; p<0.05) and leptin/PRL (r=0.51; p<0.05) links were also present. In the group C the leptin/SHGB relation (r=-0.56; p<0.02) only remained and an association between insulin and leptin was found (r=0.48; p<0.05). The body mass and BMI relation to age were again present only in all 86 women (r=0.30; p<0.002: r=0.36; p<0.001 resp.). Having split the women into groups, these links either disappeared or became inverse (rC=-0.39; p<0.05). Taking into consideration age/leptin relation in all women, the division according to the menopausal status revealed the direct relation in premenopausal women (n=29; r=0.43; p<0.02) and a reverse one in postmenopausal women (n=38; r=-0.32; p<0.05). The plasma leptin level was the highest (p<0.001) in group C (23.2+/-10.4 microg/l) and the lowest was found in the group A (8.9+/-4.1 microg/l). That corresponded with the differences in mean body mass index and mean body mass. The stepwise multiple regression revealed that body mass index accounted for 31% (p<0.001) and plasma SHBG level accounted for 17.7% (p<0.02) of plasma leptin variance in all women. In the group A body mass and age together accounted for 61% (p<0.01) and estradiol alone accounted for 44% (p<0.02) of plasma leptin variance. In the group B insulin alone accounted for 39% (p<0.05) and together with testosterone accounted for 46% (p<0.05) of plasma leptin variance. Finally in obese women none of the evaluated parameters significantly accounted for leptin variance. CONCLUSION: The results presented in this paper confirmed the strong influence of body fat mass on serum leptin concentration. However insulin, SHBG, sex steroids as well as age may also exert secondary influence on plasma leptin level in certain groups of women.

Adult↗

[Protection against electromagnetic fields reports effects exerted on the environment].

This paper presents basic information about reports on the effects exterted on the environment. These reports are elaborated to meet the needs of administrative procedures concerning the evaluation of effects exerted on the environment and provide the basis on which decisions are made whether environmental determinants allow for issuing permission for taking up a given enterprise. The author discusses only a small part of a wider problem of the report formulation. Such issues as waste management, protection against noise, conservation of historical monuments and Natura 2000 areas are not raised.

Electromagnetic Fields↗

Exertional heat illness and environmental conditions during a single football season in the southeast.

CONTEXT: Recommendations for heat illness prevention provided by sports medicine associations do not always account for sex differences, specific age populations, regional environmental conditions, equipment worn during activity, or the athlete's size or preexisting level of fitness. OBJECTIVE: To evaluate the rate of exertional heat illness (EHI) among collegiate football athletes and to monitor environmental conditions during American football practice for a 3-month period. DESIGN: Epidemiologic study in which we reviewed the occurrence rates of EHI and wet bulb globe temperature readings during a 3-month period of American collegiate football practice sessions. SETTING: Five universities in the southeastern region of the United States. PATIENTS OR OTHER PARTICIPANTS: Collegiate football players at the 5 universities. MAIN OUTCOME MEASURE(S): Wet bulb globe temperatures were recorded from August through October 2003, at the beginning, middle, and end of each practice session. The EHIs were identified and recorded, and athlete-exposures (AEs) were calculated. RESULTS: A total of 139 EHIs and 33 196 AEs were reported (EHI rate = 4.19/1000 AEs). The highest incidence of EHIs was in August (88%, EHI rate = 8.95/1000 AEs) and consisted of 70% heat cramps (6.13/1000 AEs), 23% heat exhaustion (2.06/ 1000 AEs), and 7% heat syncope (0.58/1000 AEs). No cases of heat stroke or hyponatremia were identified. The highest risk of EHI occurred during the first 3 weeks of the study; mean wet bulb globe temperature declined significantly as the study continued ( P < .001). Temperatures in the final 5 weeks of the study were significantly cooler than in the first 5 weeks ( P < .05). CONCLUSIONS: Heat cramps were the most common EHI and occurred most often during the first 3 weeks of practice. Athletic trainers should take all necessary preventive measures to reduce the risk of EHI.

Journal Article↗

Berberine, a natural cholesterol reducing product, exerts antitumor cytostatic/cytotoxic effects independently from the mevalonate pathway.

The aim of this study was to investigate the role of the mevalonate pathway in the cytostatic/cytotoxic effects of berberine, a natural plant alkaloid that reduces cholesterol concentration. Berberine as well as lovastatin, an inhibitor of the mevalonate pathway, exerted dose-dependent cytostatic/cytotoxic effects against human breast cancer cells (MDA-MB231). Although the mevalonate pathway metabolites (mevalonic acid, farnesyl pyrophosphate, geranylgeranyl pyrophosphate) effectively reversed cytostatic/cytotoxic effects of lovastatin against MDA-MB231 cells, they were not effective in influencing the cytostatic/cytotoxic effects of berberine. The cytostatic/cytotoxic effects of berberine do not seem to result from inhibition of the mevalonate pathway.

Anticholesteremic Agents↗

[Parenteral magnesium sulfate exerts no central anticonvulsant action].

It was said that parenteral magnesium (MS) had a central anticonvulsant action responsible for controlling seizures in eclampsia of pregnancy. The present study was carried out to examine this statement. In conscious rabbits, MS 214 mg.kg-1 iv quickly relieved them from convulsion induced by sc pentylenetetrazol, yet spikes of high frequency in electrocorticogram burst inceasingly. Judging from electrocorticogram changes, MS 220 mg.kg-1 iv did not raise the electroshock seizure threshold. In mice, MS 430 mg.kg-1 did not significantly increase the LD50 of ip pentylenetetrazol. However, in anesthetized rats, MS 250 mg.kg-1 ip lowered the hypertensive response to angiotensin amide and norepinephrine. These results indicated that parenterally administered MS exerted no demonstrable central anticonvulsant action, and its benefits gained in the treatment of eclampsia of pregnancy might derive from its peripheral action, such as reduction of vascular response to pressor substances.

Animals↗

Alprazolam enhances the antibacterial activity exerted by normal human peripheral blood lymphocytes.

The effects of two benzodiazepines, diazepam and alprazolam, have been evaluated on the in vitro antibacterial activity exerted by human peripheral blood lymphocytes (PBL). Results demonstrate that diazepam has no influence on this PBL function, while alprazolam is able to enhance this activity in six out of nine normal donors considered. The possible therapeutical implications of these data are discussed.

Adjuvants, Immunologic↗

[Studies on the response of epithelial cells of the hard palate to prolonged pressure exerted by prosthesis].

Microscopic examination was done of biopsy material of hard palate mucosa in healthy subjects with normal teeth and in edentulous patients with a long history of complete upper prostheses. The examination in transmission electron microscope included cells of the multilayer flat-cell epithelium of the mucosa covering the hard palate. Isolated cilia were found in the cells of the germinative layer and in the lamina propria of the mucosa where they penetrated from the epithelium across the basement membrane. The cilia were present in a significantly higher number of cells in hard palate epithelium subjected to long-term pressure exerted by the prosthesis. On the basis of observations of the structure of cilia and its environment one may assume that this apparatus may serve as an epithelial receptor of local changes produced by long-term and changing pressure of the mucosa through the mediation of masticatory forces transmitted onto the mucosa by the plate of the prosthesis.

Biopsy↗