Daily hyperhydration effect on electrolyte deficiency of endurance-Trained subjects during prolonged hypokinesia

The aim of this study was to evaluate the effect of a daily intake of fluid and salt supplementation (FSS) on the deficiency of electrolytes, which is characterized by higher rather than lower plasma concentration of electrolytes during prolonged hypokinesia (HK) (decreased number of km taken per day). Forty long distance runners aged 22–25 yr with a peak V0₂ 65.4 mL min^-1 kg^-1 with an average 14.2 km d running distance were selected as subjects. They were equally divided into four groups: 1) unsupplemented control subjects (UCS); 2) unsupplemented hypokinetic subjects (UHS); 3) supplemented hypokinetic subjects (SHS), and 4) supplemented control subjects (SCS). During the investigation of 364 d, groups 2 and 3 maintained an average running distance of less than 4.7 km per day, groups 1 and 4 did not experience any modification in their normal training routines and diets. During the preexperimental period of 60 d and during the experimental period of 364 d urinary excretion of electrolytes and concentrations of sodium, potassium, calcium, and magnesium in plasma were determined. Whole blood hemoglobin, hematocrit index, plasma osmolality, and plasma protein concentration were measured. In the UHS plasma concentration of electrolytes and urinary excretion thereof, fluid elimination, hematocrit, whole blood hemoglobin, plasma osmolality, and plasma protein concentration increased significantly (p < 0.05) when compared with the UCS, SCS, and SHS groups. In the SHS plasma concentration of electrolytes and urinary excretion thereof, fluid excretion, whole blood hemoglobin, hematocrit, plasma osmolality, and plasma protein concentration decreased when compared with the UHS and increased insignificantly when compared with the UCS and SCS groups. It was concluded that FSS may be used to prevent or minimize electrolyte deficiency in endurance-trained volunteers during prolonged restriction of muscular activity.     

Comparative study and meta-analysis of meta-analysis studies for the correlation of genomic markers with early cancer detection

A large number of common disorders, including cancer, have complex genetic traits, with multiple genetic and environmental components contributing to susceptibility. A literature search revealed that even among several meta-analyses, there were ambiguous results and conclusions. In the current study, we conducted a thorough meta-analysis gathering the published meta-analysis studies previously reported to correlate any random effect or predictive value of genome variations in certain genes for various types of cancer. The overall analysis was initially aimed to result in associations (1) among genes which when mutated lead to different types of cancer (e.g. common metabolic pathways) and (2) between groups of genes and types of cancer. We have meta-analysed 150 meta-analysis articles which included 4,474 studies, 2,452,510 cases and 3,091,626 controls (5,544,136 individuals in total) including various racial groups and other population groups (native Americans, Latinos, Aborigines, etc.). Our results were not only consistent with previously published literature but also depicted novel correlations of genes with new cancer types. Our analysis revealed a total of 17 gene-disease pairs that are affected and generated gene/disease clusters, many of which proved to be independent of the criteria used, which suggests that these clusters are biologically meaningful.     

Blood urea content changes in man under hypokinesia

It has been demonstrated that hypokinesia (diminished muscular activity) leads to an increase in blood urea content in man. Against this background the objective of this investigation was to determine blood urea content under hypokinesia (HK) on 17 physically healthy men aged 19-23 yr. They were divided into three groups: the 1st group (5 men) was examined under HK, the 2nd group (4 men) was studied during the background period (BGP) as well as in the readaptation period (RTP), and the 3rd group (8 men) was placed under ordinary conditions and served as control. For the simulation of the hypokinetic effect the men were kept under a rigorous bed rest regime for 16 days. Blood urea, blood creatinine, urine urea, and urine creatinine were measured. The results were processed statistically. The most pronounced increased urea content was observed in the men with an initial low concentration (3.3-4.2 mmole/liter). Variations in the urea concentration were analogous and manifested a reduction during the initial days and an elevation thereafter. Creatinine excretion and clearance were reduced uniformly and significantly during the initial 10 days of HK. It was concluded that diminished muscular activity induced an increase in urea content and a decrease in creatinine clearance in man.     

Calcium supplementation effect on calcium balance in endurance-trained athletes during prolonged hypokinesia and ambulatory conditions

Calcium (Ca) supplements may be used to normalize Ca-balance changes but little is known about the effect of Ca supplements on Ca balance during hypokinesia (decreased kilometers per day). The aim of this study was to evaluate the effect of daily intakes of Ca supplements on Ca balance during hypokinesia (HK). Studies were done during 30 d of a pre-HK period and during 364 d of a HK period. Forty male athletes aged 23–26 yr were chosen as subjects. They were divided equally into four groups: unsupplemented ambulatory control subjects (UACS), unsupplemented hypokinetic subjects (UHKS), supplemented hypokinetic subjects (SHKS), and supplemented ambulatory control subjects (SACS). The SHKS and UHKS groups were kept under an average running distance of 0.7 km/d. In the SHKS and SACS groups supplemented with 35.0 mg Ca lactate/kg body weight. Fecal Ca loss, urinary excretion of Ca and phosphate (P), serum concentrations of ionized calcium (Ca_I) total Ca, P, and Ca balance, intact parathyroid hormone (iPTH) and 1,25 dihydroxyvitamin D (1,25(OH)2D), anthropometric characteristics and peak oxygen uptake were measured. Fecal Ca excretion, urinary Ca and P excretion, serum Ca_I, total Ca, and P concentration, and negative Ca balanced increased significantly (p ≤ 0.01) in the SHKS and UHKS groups when compared with the SACS and UACS groups. Serum, urinary, and fecal Ca changes were much greater and appeared much faster in the SHKS group than in the UHKS group. Serum iPTH and 1,25 (OH)2 D, body weight, and peak oxygen uptake decreased significantly (p ≤ 0.01) in the SHKS and UHKS groups when compared with the SACS and UACS groups. In contrast, the corresponding parameters remained stable in the SACS and UACS groups when compared with the baseline control values. It was concluded that during prolonged HK, urinary and fecal Ca excretion and serum Ca concentration increased significantly despite the presence of a negative Ca balance; thus, Ca supplements cannot be used to normalize negative Ca balance during prolonged HK.     

Serum, urinary, and fecal calcium changes in trained and untrained subjects during prolonged hypokinetic and ambulatory conditions

Electrolyte metabolism undergoes significant changes in trained subjects, but it is unknown if it undergoes significant changes in untrained subjects during hypokinesia (decreased movement). The aim of this study was to measure calcium (Ca) changes in trained and untrained subjects during prolonged hypokinesia (HK). Studies were done during 30 d of a pre-HK period and 364 d of a HK period. Forty male trained and untrained volunteers aged 23–26 yr were chosen as subjects. All subjects were equally divided into four groups: trained ambulatory control subjects (TACS), trained hypokinetic subjects (THKS), untrained hypokinetic subjects (UHKS), and untrained ambulatory control subjects (UACS). The THKS and UHKS groups were kept under an average running distance of 0.7 km/d. Fecal Ca excretion, urinary Ca and magnesium (Mg) excretion, serum ionized calcium (Ca_I), Ca, Mg, intact parathyroid hormone (iPTH) and 1,25 dihydroxyvitamin D [1,25 (OH)2 D] concentration, body weight, and peak oxygen uptake were measured. Fecal Ca loss, urinary Ca and Mg excretion, and serum Ca_I, Mg, and Ca increased significantly (p ≤ 0.01), whereas serum iPTH and 1,25 (OH)2 D concentration body weight and peak oxygen uptake decreased significantly (p ≤ 0.01) in the THKS and UHKS groups when compared with the TACS and UACS groups. The measured parameters were much greater and much faster in the THKS group than in the UHKS group. By contrast, the corresponding parameters did not change significantly in the TACS and UACS groups when compared with the baseline control values. It was concluded that prolonged HK induces significant fecal, urinary, and serum Ca changes in the hypokinetic subjects when compared with control subjects. However, fecal, urinary, and serum Ca changes were much greater and appeared much faster in the THKS group than the UHKS group.     

Potassium loading effect on potassium balance in athletes during prolonged restriction of muscular activity

Negative potassium balance during hypokinesia (decreased number of kilometers taken/day) is not based on the potassium shortage in the diet, but on the impossibility of the body to retain potassium. To assess this hypothesis, we study the effect of potassium loading on athletes during prolonged hypokinesia (HK). Studies were done during 30 d of a pre-HK period and during 364 d of an HK period. Forty male athletes aged 23–26 yr were chosen as subjects. They were divided equally into four groups: unloaded ambulatory control subjects (UACS), unloaded hypokinetic subjects (UHKS), loaded hypokinetic subjects (LHKS), and loaded ambulatory control subjects (LACS). For the simulation of the hypokinetic effect, the LHKS and UHKS groups were kept under an average running distance of 1.7 km/d. In the LACS and LHKS groups, potassium loading tests were done by administering 95.35 mg KC1 per kg body weight. During the pre-HK and HK periods and after KC1 loading tests, fecal and urinary potassium excretion, sodium and chloride excretion, plasma potassium, sodium and chloride concentration, and potassium balance were measured. Plasma renin activity (PRA) and plasma aldosterone concentration was also measured. Negative potassium balance increased significantly (p < -0.01) in the UHKS and LHKS groups when compared with the UACS and LACS groups. Plasma electrolyte concentration, urinary electrolyte excretion, fecal potassium excretion, PRA, and PA concentration increased significantly (p ≤ 0.01) in the LHKS and UHKS groups when compared with LACS and UACS groups. Urinary and fecal potassium excretion increased much more and much faster in the LHKS group than in the UHKS group. By contrast, the corresponding parameters change insignificantly in the UACS and LACS groups when compared with the base line control values. It was concluded that urinary and fecal potassium excretion increased significantly despite the presence of negative potassium balance; thus, negative potassium balance may not be based on potassium shortage in the diet because of the impossibility of the body to retain potassium during HK.     

Phosphate-loading tests influences on endurance-trained volunteers during restriction of muscular activity and chronic hyperhydration

The purpose of this investigation was to determine whether negative phosphate balance, which is developed during hypokinesia (a decreased number of walking steps/d) could be reversed with daily supplementation with phosphate, fluid, and salt (FSS). The studies on hypokinesia (HK) were performed for 364 d on 30 endurance-trained male volunteers in the age range of 23–26 yr, with an average maximum oxygen uptake, MOU, of 65 mL/kg min. All subjects were divided into three equal groups: Ten volunteers were placed on a continuous regime of exercise of 14.4 kmJd at 10,000 steps/d and served as controls. Ten volunteers were subject to continuous HK without FSS and were considered as the hypokinetic subjects (HS). The remaining subjects were under continuous HK and FSS and were considered as the hypokinetic, hyperhydrated subjects (HHS). The three groups were on a diet that averaged 2620 cal/d and contained 1.7 g calcium, 1.6 g phosphate, and 5.6 g sodium chloride. For simulation of the hypokinetic effect, the HS and HHS groups were kept continuously under 2.9 km/d (3000 walking steps/d) for the duration of the study. Prior to exposure to HK, all volunteers were on the same exercise regime as the controls. During a 60-d pre-HK period and during the remainder of the study, phosphate-loading tests, urinary and plasma phosphate concentrations were performed in all subjects. In the HHS group, plasma phosphate concentration and urinary excretion of phosphate were decreased, while in the HS group these values increased after phosphate loading. Based on our results, we concluded that chronic hyperhydration and phosphate supplementation may be used to minimize phosphate losses in endurance-trained volunteers during prolonged restriction of muscular activity.     

Down-modulation of epidermal growth factor receptor accompanies TNF-induced differentiation of the DiFi human adenocarcinoma cell line toward a goblet-like phenotype

Although the biologic response modifier tumor necrosis factor-alpha (TNF) is a known differentiation Inducer in hematopoietic cells, its role in differentiation of other tissue types has yet to be elucidated. In the studies presented here, TNF treatment of the human rectal adenocarcinoma cell line, DiFi, elicits characteristics of early stage differentiating, mucin-producing colonocytes. Not only are TNF-treated DiFi cells growth-inhibited by TNF, but they also display a unique morphology. Additionally, TNF treatment of DiFi cells enhances > fivefold the expression of high molecular weight mucin glycoproteins, as measured by [¹²⁵I]-wheat germ agglutinin (WGA) binding and the human milk fat globule-1 (HMFG-1) anti-MUC1 antibody reactivity. The induction of these differentiation characteristics correlates with novel alterations in epidermal growth factor receptor (EGF-R). Following 5-day TNF treatment of DiFi cultures, EGF receptor levels, kinase autophosphorylation activity, and receptor tyrosine phosphorylation are reduced by > fourfold. The establishment of a model system in which goblet-like cell characteristics and alterations in a growth factor receptor can be induced in vitro may be potentially useful in studying the underlying mechanisms of colonic epithelial cell proliferation and differentiation. © 1993 Wiley-Liss, Inc.     

DNA interactions of pH-sensitive, antitumor bis(aminoalcohol)dichloroplatinum(II) complexes

(SP-4-2)-Bis(2-aminoethanol)dichloroplatinum(II) (KP1356) and (SP-4-2)-bis[(R)-(-)-2-aminobutanol)]dichloroplatinum(II) (KP1433) are promising cytotoxic agents capable of changing their chemical structure depending on the pH value. On the basis of this, they are supposed to be active only in or preferentially in hypoxic tumors with low pH. In this study, we investigated the kinetics of changes of the DNA secondary structure, of the DNA modification degree, and of the formation of interstrand cross-links caused by these complexes in comparison to the parental compound cis-diamminedichloroplatinum(II) (cisplatin). All examinations were performed at physiological pH 7.4 and at pH 6.0 mimicking the acidified environment of many tumor tissues. In general, cisplatin displayed a higher reactivity accompanied by more pronounced DNA compaction, untwisting, and formation of interstrand cross-links at both pH values. Additionally, it was shown for the first time that cisplatin generates interstrand cross-links faster at pH 6.0 than at 7.4. However, the difference between pH 7.4 and 6.0 was much larger for KP1356 and KP1433 than for cisplatin, since they were essentially nonreactive and induced almost no secondary structures at pH 7.4, as contrasted to cisplatin. Our data suggest that formed adducts, i.e., intra- and/or interstrand cross-links, may be the sole cause of the cytotoxicity of KP1356 and KP1433 at pH 6.0. The results of this study may stimulate and contribute to further improvement of these novel, specific cytotoxic drugs that are anticipated to exert their full power in the tumor while being reasonably inactive in normal tissue.     

Evidence for a LPS-binding protein in medfly hemocyte surface: mediation in LPS internalization but not in LPS signaling

A doublet of medfly hemocyte proteins with a molecular mass of about 55 and 50 kDa were precipitated with LPS. Antibodies raised against human CD14 recognize the same doublet of proteins. These results support that mammalian CD14 and the doublet of protein bands in medfly hemocytes share common epitopes. This doublet of protein bands is released from hemocytes upon LPS triggering. A portion of the released protein is clustered on the surface of a distinct hemocyte type and the other remains soluble. The membrane-bound LPS-binding protein is involved in LPS internalization and Escherichia coli phagocytosis but not in LPS signaling.