Fluid intake at work in foresters working in different thermal conditions.

The primary aim of this study was to assess the impact of fluid intake on hydration status indices in men at work. The secondary aim was to determine the type of fluids drunk at work in different thermal conditions. Fifty-nine male foresters were examined before and after one working day during summer, autumn, and winter. Before and after work, urine and blood samples were obtained from foresters. Immediately after a shift, participants completed a questionnaire regarding fluid intake during one working day. The amount of fluid consumed affects the hydration urine indices. Urine specific gravity and urine osmolality significantly decreased with increasing fluid intake (r = - 0.385 and r = - 0.405, respectively). Moreover, an impact of season on the type of fluids consumed by workers was observed. Tea was significantly more often chosen by workers to drink in winter (68%) than in summer (32%) (p = 0.026). The consumption of any non-alcoholic fluids contributes to the daily total water intake, but it is necessary to create individualized fluid replacement plans. Workers should know how much and what types of drinks to consume at work.

Cardiac axis shift within the cardiac cycle of normal fetuses and fetuses with congenital heart defect.

OBJECTIVES: To investigate changes in the cardiac axis (CAx) within the cardiac cycle of normal fetuses and fetuses with congenital heart defects (CHD). METHODS: This was a retrospective case-control study in which stored videoclips of four-chamber views from 527 prenatal ultrasound examinations performed at 18 + 0 to 36 + 6 weeks of gestation were reviewed. Among the ultrasound scans included, 287 were of normal fetuses (controls) and 240 were of fetuses with CHD. In each case, the CAx was measured at end systole (just before the atrioventricular (AV) valve opened) and at end diastole (just before the AV valve closed). CAx measurements of fetuses with CHD were compared to those of controls. RESULTS: The mean CAx in the control group was 45.9 ± 8.5° at end systole and 38.3 ± 8.4° at end diastole (P < 0.001), resulting in an average difference of 7.6 ± 3.2°. The mean CAx in fetuses with CHD was 53.4 ± 17.8° at end systole and 47.5 ± 17.3° at end diastole (P < 0.001), resulting in an average difference of 5.9 ± 6.3°. However, in some forms of CHD, such as hypoplastic left heart syndrome and L-transposition of the great arteries, the CAx was greater at end diastole than at end systole, with a difference of more than 5°. In 21.3% of control fetuses, there was a CAx shift within the cardiac cycle of ≥ 10°. Abnormal CAx measured at end systole was strongly associated with CHD. CONCLUSIONS: Measurement of the CAx at end systole provides values that differ from those when measured at end diastole, in both normal fetuses and those with CHD. We recommend that the CAx be measured at end systole as a greater proportion of fetuses with CHD and fewer normal fetuses have an abnormal CAx at this stage compared to at end diastole. The occurrence of an abnormal CAx and the CAx shift within the fetal cardiac cycle depend on the type of CHD.

Indications for caesarean sections at ≥34 weeks among nulliparous women and differential composite maternal and neonatal morbidity.

OBJECTIVE: To compare composite maternal and neonatal morbidities (CMM, CNM) among nulliparous women with primary indications for caesarean section (CS) as acute clinical emergency (group I; ACE), non-reassuring fetal heart rate (group II) and arrest disorder (group III). DESIGN: A multicentre prospective study. SETTING: Nineteen academic centres in the USA, with deliveries in 1999-2002. POPULATION: Nulliparous women (n = 9829) that had CS. METHODS: Nulliparous women undergoing CS for three categories of indications were compared using logistic regression model, adjusted for five variables. MAIN OUTCOME MEASURES: CMM was defined as the presence of any of the following: intrapartum or postpartum transfusion, uterine rupture, hysterectomy, cystotomy, ureteral or bowel injury or death; CNM was defined as the presence of any of the following: umbilical arterial pH <7.00, neonatal seizure, cardiac, hepatic, renal dysfunction, hypoxic ischaemic encephalopathy or neonatal death. RESULTS: The primary reasons for CS were ACE in 1% (group I, n = 114) non-reassuring FHR in 29% (group II; n = 2822) and failed induction/dystocia in the remaining 70% (group III; n = 6893). The overall risks of CMM and CNM were 2.5% (95% confidence intervals, CI, 2.2-2.8%) and 1.9% (95% CI 1.7-2.2), respectively. The risk of CMM was higher in group I than in group II (RR 4.1, 95% CI 3.1, 5.3), and group III (RR 3.2, 95% CI 2.7, 3.7). The risk of CNM was also higher in group I than in group II (RR 2.8, 95% CI 2.3, 3.4) and group III (RR 14.1, 95% CI 10.7, 18.7). CONCLUSIONS: Nulliparous women who have acute clinically emergent caesarean sections are at the highest risks of both composite maternal and neonatal morbidity and mortality.

Long-term hypoxia alters calcium regulation in near-term ovine myometrium.

Previous studies showed that long-term hypoxia (LTH) during pregnancy alters myometrial contractility. The present study was designed to test the hypothesis that LTH during pregnancy suppresses myometrial contractility in sheep by affecting the calcium signaling cascade. Pregnant sheep were maintained at high altitude (3820 m) from Day 30 to Day 139 of gestation, when the animals were killed for collection of myometrial tissue. Tissue was also collected from age-matched, normoxic controls. Circular and longitudinal layers were separated, and strips from each layer were mounted in a muscle bath. After pretreatment with 10(-8) M oxytocin, the strips were exposed to increasing half- or quarter-log doses of nifedipine (L-type calcium-channel blocker), ruthenium red, ryanodine (blockers of inositol 1,4,5-trisphosphate-insensitive calcium stores), or 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (NCDC; phospholipase C inhibitor). Area under the contraction curve was analyzed, and pD(2) (log of concentration yielding 50% of maximum response) values and maximum relaxation responses were calculated. The maximum relaxation response to nifedipine was increased in both longitudinal (P < 0.01) and circular (P < 0.05) myometrial layers from LTH compared to control tissue, whereas no difference was observed in response to ruthenium red or ryanodine. The maximum relaxation response to NCDC was lower in the LTH circular layer (P < 0.05). Together, these data are indicative of an increase in the dependence of ovine uterine smooth muscle on extracellular calcium influx through the L-type, voltage-gated calcium channels following LTH. This appears to occur not through an increase in L-type calcium channels but, rather, through a possible decline in importance of the oxytocin-induced, phospholipase C-mediated pathway, resulting in a greater proportion of extracellular calcium contributing to contraction. Layer-dependent differences also exist between the circular and longitudinal myometrium in response to phospholipase C inhibition.

Long-term hypoxia changes myometrial responsiveness and oxytocin receptors in the pregnant ewe: differential effects on longitudinal versus circular smooth muscle.

Previous studies from our laboratory demonstrated that long-term hypoxia (LTH) altered in vitro contractile responses to oxytocin in full-thickness myometrial strips from pregnant sheep. The present study was designed to determine, first, if the reduced contractile response to oxytocin following LTH is the result of combined effects on longitudinal and circular smooth muscle or if the effect is specific to a single muscle layer and, second, if the reduced contractile response to oxytocin following LTH is caused by changes in oxytocin-receptor protein. Pregnant ewes were maintained at high altitude (3820 m) from Day 30 to Days 137-142 of gestation, when the ewes were killed for collection of myometrial tissue. Tissue was also collected from age-matched, normoxic controls. Longitudinal and circular layers were separated, length-tension curves generated to determine optimal resting tension, and all strips exposed to increasing half-log doses of oxytocin ranging from 10-12 to 10-6.5 M. The expression of oxytocin-receptor protein was measured using Western blot analysis. We found that LTH did not affect KCl-induced contraction of either smooth muscle layer, whereas the sensitivity of both myometrial layers to oxytocin was altered. A decreased maximum contractile response of the circular layer to oxytocin was also observed. Additionally, LTH decreased expression of oxytocin-receptor protein in the circular layer and increased levels in the longitudinal layer. Results from the present study indicate that LTH alters contractile responses and oxytocin-receptor protein expression in a layer-specific manner in the pregnant sheep myometrium.

[The effect of cocarboxylase treatment on erythrocyte transketolase and blood thiamine in patients with end stage renal disease undergoing maintenance hemodialysis]. / Wplyw leczenia kokarboksylaza na aktywnosc transketolazy w erytrocytach i stezenie tiaminy we krwi u chorych ze schylkowa niewydolnoscia nerek, leczonych powtarzana hemodializa.

The depressed ETKA in ESRD patients is supposed to be caused and/or aggravated by several factors among which the diminished content of thiamine in blood and/or disturbances of thiamine utilization seem to play the major role. This role stems from the fact that thiamine acts as the cofactor of transketolase. In order to check the therapeutic significance of this relationship we introduced the thiamine pyrophosphoric acid ester chloride (Cocarboxylasum-CC) administration in 25 patients (mHD + CC). Immediately after each HD performance CC was given i.v. during 12 weeks in a doses of 5 mg/kg b.w., 3 times a week. The blood for ETKA value, free and total thiamine in plasma and erythrocytes, as well as, the total protein and albumins/globulins index investigation was drawn before, after 6 and 12 weeks of CC administration, and 3 months after cessation of this therapy. In 10 patients, on maintenance HD nontreated by CC (mHD), the blood was drawn at the same time intervals. Normal values we obtained from 15 healthy volunteers. For ETKA evaluation photocolorimetric method was used, thiamine content in blood was estimated by fluorimetric method. At the beginning of the study the mean value of ETKA, in two examined groups, was found statistically decreased (p < 0.01) when compared with normals. Mean values of thiamine in plasma and erythrocytes were lower but did not differ significantly from those in normals. After 6 weeks of CC administration ETKA value increased, but only after 12 weeks it increased significantly (p < 0.01), reaching normal value. On the other hand, striking increase in plasma thiamine and erythrocyte thiamine levels was observed after 6 weeks of CC administration already (p < 0.01). Three months after cessation of CC administration significant decrease in ETKA value and thiamine level in blood was observed (p < 0.01). ETKA returned to lower value than in normals even in the presence of still high thiamine levels in blood. In mHD patients nontreated by CC the ETKA value and thiamine levels in blood did not change significantly during all periods of study. The nutritional status assessed by total protein and albumins/globulins index did not change in both groups through the study. We conclude, the administration of high doses of CC to ESRD patients on maintenance hemodialysis HD was successful in terms of increasing ETKA value and thiamine levels in blood without any side effects. Thus, supplementation with large doses of CC deserves further study because it promises to be another adjunct in the treatment of potential thiamine deficiency and metabolic disturbances in the course of dialysotherapy.

[Influence of maternal smoking on kynurenic acid concentrations in umbilical cord blood]. / Ocena wplywu palenia papierosów przez ciezarna na stezenia kwasu kynureninowego we krwi pepowinowej.

The aim of the study was to evaluate the influence of maternal smoking on kynurenic acid (KYNA) levels in venous and arterial umbilical cord blood of neonates. Statistically significant lower concentration of KYNA in umbilical arterial blood of smoking mothers neonates was observed. The lower levels of KYNA in blood may reflect the smaller resistence of neuronal tissue to damages under hypoxic-ischemic conditions in neonates affected during intrauterine life by smoking.

Influence of intracerebroventricular administration of tetanus toxin on experimental seizures and protection afforded by some antiepileptic drugs in mice.

The dose to the intracerebroventricularly administered (i.c.v.) tetanus toxin (Tetx) evoking the death of 50% of experimental mice (LD50) was estimated to be 18.0 (11.5-28.2) times the minimal lethal dose (MLD). MLD is defined as the lowest does of Tetx necessary to kill a 20-g albino mouse within 96 h after intraperitoneal treatment. Tetx (0.25 and 0.5 LD50) increased the convulsive threshold of electric current from 24 to 96 and 120 h, respectively, following i.c.v. administration. Both doses of Tetx diminished convulsant potencies of pentylenetetrazole, bicuculline, aminophylline and pilocarpine 24 h after application. At the same time Tetx (0.5 LD50) increased the protection afforded by carbamazepine, valproate, phenobarbital and diazepam in maximal electroshock (MES) by approximately 36, 11, 21 and 26%, respectively, without affecting total blood plasma levels of antiepileptic drugs. No marked changes in gamma-aminobutyric acid (GABA) concentration and total activity of L-glutamic acid decarboxylase (GAD) assessed in the whole-brain homogenates resulted from Tetx treatment. Our results seem to indicate that low doses (< LD50) of i.c.v. administered Tetx may lead to a relative prevalence of inhibitory over excitatory processes in the central nervous system suggesting a complex action of Tetx at the neuronal level.

Role of voltage dependent calcium channels and cholinergic receptors in the convulsant action of BAY k-8644.

The study was designed to investigate the effects of administration of cholinomimetic agents and nifedipine on seizures induced by BAY k-8644 in rats. Injection of pilocarpine (3 mg/kg) increased seizures induced by BAY k-8644 (2 mg/kg). Administration of nifedipine (10 mg/kg) did not affect the convulsions and mortality elicited by coadministration of BAY k-8644 and pilocarpine. However, the facilitating effect of pilocarpine on BAY k-8644-induced seizures was fully prevented by pretreatment of rats with a cholinergic antagonist atropine (5 mg/kg). No similar effects were observed after injection of another cholinomimetic agent physostigmine (0.3 mg/kg). This finding implies, that facilitation of convulsant action of BAY k-8644 by pilocarpine may be related to activity of cholinergic system, but not strictly to activity of voltage dependent calcium channels.

Synthesis and pharmacological evaluation of N-aryl(pyrimidinyl) piperazinylalkyl (hydroxyalkyl) derivatives of 1,2,3,4-tetra- and 1,2,3,4,5,6-hexahydropyrido[3,4-d]pyridazines.

The synthesis of N-aryl(pyrimidinyl)piperazinylalkyl(hydroxyalkyl) derivatives of 1,4-dioxo(1,4,5-trioxo)-1,2,3,4-tetra (and 1,2,3,4,5,6-hexa)hydropyrido[3,4-d]pyridazines is described. Some of them show biological activity in the preliminary pharmacological tests.

Intracerebroventricular pertussis toxin enhances sensitivity to chemical convulsants and decreases the protective efficacy of carbamazepine in mice.

The effects of pretreatment with pertussis toxin on pentylenetetrazole-, bicuculline-, aminophylline- and pilocarpine-induced seizures were investigated in mice. In animals treated intracerebroventricularly with pertussis toxin (0.5 microgram animal-1 120 h prior to testing), the CD50 (convulsive dose in 50%) values were considerably decreased in comparison with the CD50 in sham-treated animals. CD50 values of pentylenetetrazole, bicuculline, pilocarpine and aminophylline were calculated to be 39.9, 2.0, 262 and 141 mg kg-1, whereas they were calculated to be 57.7, 2.7, 324 and 230 mg kg-1 in sham-treated animals. The observations suggest that the enhanced sensitivity to a number of chemical convulsants irrespective of their mode of action possibly results from a functional suppression of inhibitory transmission at receptors coupled to pertussis toxin sensitive G proteins, rather than a direct action on G protein linked excitatory neurotransmission. Pertussis toxin significantly decreased the protective action of carbamazepine, increasing its ED50 (effective dose in 50%) from 14.8 to 20.1 mg kg-1 in a maximal electroshock convulsive test. It influenced the ED50 of neither diphenylhydantoin nor diazepam. The diminution of carbamazepine's efficacy might result from a summation effect of adenosine receptor antagonist properties of the drug and a suppression of transmission at adenosine receptors coupled to G proteins sensitive to pertussis toxin. Pertussis toxin pretreatment remained without any significant influence on the total plasma levels of carbamazepine, diphenylhydantoin and diazepam. This may lead to the conclusion that the interaction between pertussis toxin and carbamazepine does not seem to be of a pharmacokinetic nature and occurs probably at neuronal level.

[Content of thiamin in plasma and erythrocytes in patients with end stage renal disease]. / Zawartosc tiaminy w osoczu i erytrocytach u chorych ze schylkowa niewydolnoscia nerek.

In 68 patients with end stage renal disease (ESRD), nondialyzed-(ND)-21 treated by hemodialysis (HD)-27 or intermittent peritoneal dialysis (IPD)8 and continuous ambulatory peritoneal dialysis (CAPD)-12, we examined thiamine free (Th F) and thiamine total (Th T) content in plasma (P) and erythrocytes (E). 20 healthy volunteers (HV) served as a control group. Thiamine content in plasma and in hemolysate was assessed by fluorimetric method according to Blum and Merkel. In all patients the mean Th FP, Th TP, and Th FE, Th TE levels were decreased in comparison to HV. Mean level of Th FE in ND and IPD was significantly decreased (p < 0.05) in comparison to Th FE to HV and to patients treated by HD or CAPD. Mean level of Th FP was the lowest in IPD group, but did not differ significantly from Th FP in ND, HD and CAPD). In IPD patients mean level of Th TE was the lowest and differed significantly (p < 0.05) from that in HD and CAPD groups. The lowest mean level of Th TP we found in CAPD patients. There was significant difference with it in ND and HV group (p). Patients treated by HD and CAPD presented almost normal levels of Th FE and Th TE. The highest mean levels of Th FP and Th TP were found in ND patients. We suggest the need of thiamine supplementation in ESRD patients especially in those treated by dialysis. The supplementation of thiamine is needed particularly in patients on peritoneal dialysis.

NG-nitro-L-arginine sensitizes mice to 4-aminopyridine-induced seizures.

We investigated the influence of NG-nitro-L-arginine (NNA), the inhibitor of nitric oxide synthese, on seizures induced by 4-aminopyridine (4-AP), the K+ channel antagonist, in mice NNA (5, 10 and 40 mg/kg, i.p.) significantly reduced the respectives CD50 of 4-AP from 9.0 to 7.6, 7.5 and 6.8 for clonic seizures, and from 9.2 to 7.7, 7.5 and 6.9 for tonic seizures and death. Lower doses of NNA (1.0 and 2.5 mg/kg) had no effect on 4-AP-induced convulsions and lethality. Our results indicate that 4-AP-induced seizures may be, at least in part, dependent on nitric oxide level.

Effect of nifedipine on lithium-pilocarpine-induced seizures in the rats.

Recent studies have shown that lithium pretreatment of rats potentiates the convulsant effect of pilocarpine. A large body of evidence support the hypothesis that calcium channel antagonists possess antiepileptic properties in various models of epilepsy. This study was designed to investigate effect of calcium channel antagonist, nifedipine on lithium-pilocarpine-induced convulsions in rats. Pretreatment of rats with nifedipine (5 or 10 mg/kg) as well as with a calcium channel agonist BAY k-8644 (2 mg/kg) increased convulsant effect induced by lithium and pilocarpine. The facilitating effect of nifedipine on lithium-pilocarpine-induced convulsions was prevented by pretreatment with a cholinergic antagonist atropine. It can be concluded that nifedipine facilitates convulsions in lithium-pilocarpine model of epilepsy and that cholinergic system may be involved in this effect.

The influence of antineoplaston A5 on particular subtypes of central dopaminergic receptors.

A new therapeutic strategy for the treatment of Parkinson's disease (PD) is based on providing trophic support for degenerating dopaminergic (DA) neurons. It can be accomplished by administration of neurotrophic factors, or inducing astrocytes to differentiate and produce such factors. Antineoplaston A5 (A5), which is a naturally-occurring cytodifferentiating agent, may induce astrocytes to undergo normal differetiation, produce neurotrophic factors and alleviate the symptoms of PD. This paper describes studies on the influence of A5 on subtypes of central DA receptors by measuring the potency of haloperidol catalepsy in rats. A5, D1 agonist, and D1 D2 antagonists were given i.p. and D2 agonist s.c. for three consecutive days. Haloperidol catalepsy was measured by the method of Costall and Nylor. The degree of catalepsy was assessed every 30 min for 24 h and statistically evaluated using the Student's t-test. The results confirmed that A5 significantly attenuated catalepsy and stimulates dopamine D2 receptors. It reverses catalepsy induced by haloperidol and D2 antagonists, but increases cataleptogenic activity if given in combination with the D2 agonist. This leads to the conclusion that A5 as a naturally-occurring agent neutralizes both hyper- and hypoactivity of central dopaminergic structures. Besides possible use as an antiparkinsonism agent, A5 may find application in the treatment of other disturbances of dopaminergic transmission.

[The influence of intermittent peritoneal dialysis on free and total thiamine concentration in plasma and erythrocytes of patients with end stage renal disease]. / Wplyw przerywanej dializy otrzewnowej na stezenie tiaminy wolnej i calkowitej w osoczu i erytrocytach u chorych ze schylkowa niewydolnoscia nerek.

The concentration of free and total thiamine in plasma (PFTh and PTTh) and in erythrocytes (EFTh and ETTh) was determined in 20 healthy volunteers and in 8 patients suffering from ESRD treated (60 hrs/week) with IPD. Venous blood for determinations was taken immediately before and at the end of the subsequent 20-hrs PD as well as, after 12 and 48 hrs elapsed from the completion of this procedure. Thiamine was determined using fluorimetric method. Mean concentration of PFTH and PTTh as well as ETTh of patients before dialysis was found to be low, but did not differ significantly from those found in the group of healthy volunteers. Mean value of EFTh before PD was statistically lower than in normals (p < 0.05). After dialysis lasting 20 hrs a significant lowering of the concentration of PFTH (p < 0.001) and PTTh (p < 0.01) has been observed, whereas the concentration of EFTh and ETTh significantly increased (p < 0.05). After 12 and 48 hrs elapsed from the completion of dialysis a statistically significant increase in PFTh and PTTh concentration has been noted contrasting with those in EFTh and ETTh, where it felt down. Nevertheless these values in plasma and erythrocytes after 48 hrs from the completion of dialysis did not differ significantly from those found at the beginning of the determination. We conclude that IPD is a procedure exerting short-term lowering of the plasma thiamine concentration with simultaneous increase in those in erythrocytes concentration. Further studies are indispensable to clarify the problem of thiamine supplementation in patients treated with PD.