Salivary but not plasma cortisone tracks the plasma cortisol response to exercise: effect of time of day.

INTRODUCTION: The cortisol, cortisone, corticosterone, and CBG responses to exercise in the AM and PM have not been described. This study examined the response of these glucocorticoids and CBG to intense exercise in 12 endurance-trained men in plasma (Pl) and saliva (Sa). METHODS: Each subject completed treadmill exercise in the morning and evening. Paired blood and Sa samples were obtained at rest before and after exercise. RESULTS: Significant time effect existed for Pl-cortisol and Sa-cortisol from baseline in the AM and PM (p < 0.01). Pl-cortisone and CBG significantly increased in the PM (p < 0.01). Pl-corticosterone increased in the AM and PM (p < 0.01). Unlike Pl-cortisone, Sa-cortisone was significantly higher in the AM compared to the PM, increasing in the AM and PM (All p < 0.01). Strong associations were found between Pl-cortisol and Sa-cortisol (r = 0.81, p < 0.0001), Pl-cortisol and Sa-cortisone (r = 0.81, p < 0.0001). CONCLUSIONS: (1) Intense EX induces a similar increase in Pl-cortisone (~90 %) and corticosterone (~200 %) in the AM and PM, whereas exercise increases CBG in the PM, but not in the AM; (2) vigorous exercise increases Sa-cortisone; (3) Sa-cortisone and cortisol are equally strongly correlated to Pl-cortisol, suggesting a significant role for Sa-cortisone as a novel marker of free cortisol during exercise.

Natronococcus roseus sp. nov., a haloalkaliphilic archaeon from a hypersaline lake.

A novel halophilic archaeon, strain CG-1(T), belonging to the genus Natronococcus was isolated from sediment of the soda lake Chagannor in Inner Mongolia, China. The colonies of this strain were pink pigmented, the intensity of the colour decreased when the cells grew at salt saturation levels. The cells were non-motile cocci and strictly aerobic. Hypotonic treatment did not cause cell lysis, even in distilled water. Strain CG-1(T) grew at 15-30.0 % (w/v) NaCl and at 30-50 °C and pH 8.0-11.0, with optimal growth occurring at 25-30 % (w/v) NaCl, 37-45 °C and pH 9-9.5. MgCl(2) was not required for growth. Strain CG-1(T) was most closely related to the type strains of Natronococcus amylolyticus Ah-36(T), Natronococcus jeotgali B1(T) and Natronococcus occultus SP4(T), with which it shared 98.4 %, 96.2 and 95.7 % 16S rRNA gene sequence similarity, respectively. The polar lipids consisted of C(20)C(20) and C(20)C(25) derivatives of phosphatidylglycerol (PG), phosphatidylglycerol phosphate methyl ester (PGP-Me) and minor phospholipid components. No glycolipids were detected. The DNA G+C content of strain CG-1(T) was 62.1 mol%. DNA-DNA hybridization with N. amylolyticus DSM 10524(T), phylogenetically the most closely related species, was 39 %; this value showed that strain CG-1(T) constituted a different genospecies. The comparison of 16S rRNA gene sequences, detailed phenotypic characterization, polar lipid profile and DNA-DNA hybridization studies revealed that strain CG-1(T) belongs to the genus Natronococcus and constitutes a novel species for which the name Natronococcus roseus sp. nov. is proposed. The type strain is CG-1(T) (=CECT 7984(T)=IBRC-M 10656(T)=JCM 17958(T)).

Predictors of pathological gambling severity taking gender differences into account.

BACKGROUND: The current study aims to identify predictors of pathological gambling (PG) severity, taking gender differences into account, in an outpatient sample of pathological gamblers seeking treatment. METHODS: The sample for this study consisted of 103 subjects (51 women and 52 men) meeting current DSM-IV-TR criteria for PG. Linear and logistic regression analyses were used to examine different risk factors (gender, age, impulsivity, sensation seeking, self-esteem) and risk markers (depression, anxiety, gambling-related thoughts, substance abuse) as predictors of PG severity. RESULTS: Impulsivity, maladjustment in everyday life and age at gambling onset were the best predictors in the overall sample. When gender differences were taken into account, duration of gambling disorder in women and depression and impulsivity in men predicted PG severity. In turn, a high degree of severity in the South Oaks Gambling Screen score was related to older age and more familiy support in women and to low self-esteem and alcohol abuse in men. Female gamblers were older than male gamblers and started gambling later in life, but became dependent on gambling more quickly than men. CONCLUSIONS: Further research should examine these data to tailor treatment to specific patients' needs according to sex and individual characteristics.

Factor H and CFHR1 polymorphisms associated with atypical Haemolytic Uraemic Syndrome (aHUS) are differently expressed in Tunisian and in Caucasian populations.

Several polymorphisms in the complement components factor H and CFHR1 are associated with higher risk to develop atypical Haemolytic Uraemic Syndrome (aHUS) in Caucasians. We have determined the prevalence of these polymorphisms in Tunisian controls by using genetic and immunological techniques. No differences in the frequency of the factor H risk alleles c.-331C>T, c.2089A>G or c.2881G>T between Tunisian and Caucasians were found. On the contrary, the analysis of CFHR1 polymorphism revealed a higher frequency of Tunisian individuals homozygous for the CFHR1*Del (deleted) allele, and of individuals presenting the CFHR1*A phenotype. These results suggest distinct contributions of factor H and CFHR1 polymorphisms to aHUS in Tunisian and Caucasian populations.

Halorubrum aquaticum sp. nov., an archaeon isolated from hypersaline lakes.

Two halophilic archaea, strains EN-2(T) and SH-4, were isolated from the saline lakes Erliannor and Shangmatala, respectively, in Inner Mongolia, China. Cells were strictly aerobic, motile rods. Colonies were red. Strains EN-2(T) and SH-4 were able to grow at 25-50 °C (optimum 35-40 °C), with 2.5-5.0 M NaCl (optimum 3.4 M NaCl) and at pH 6.0-9.0 (optimum pH 7.5). MgCl(2) was not required for growth. Cells lysed in distilled water and the lowest NaCl concentration that prevented cell lysis was 12 % (w/v). On the basis of 16S rRNA gene sequence analysis, strains EN-2(T) and SH-4 were closely related to Halorubrum cibi B31(T) (97.9 and 98.0 % similarity, respectively), Hrr. tibetense 8W8(T) (97.3 and 97.7 %), Hrr. alkaliphilum DZ-1(T) (96.8 and 97.1 %), Hrr. luteum CGSA15(T) (96.8 and 97.0 %) and Hrr. lipolyticum 9-3(T) (96.8 and 97.0 %). DNA-DNA hybridization showed that strains EN-2(T) and SH-4 did not belong to the same species as any of these strains (≤ 45 % DNA-DNA relatedness) but that they are members of the same species (>70 % DNA-DNA relatedness). Polar lipid analysis revealed that strains EN-2(T) and SH-4 contained phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, sulfated diglycosyl diethers and several unidentified glycolipids. The DNA G+C content of both isolates was 62.1 mol%. It was concluded that strains EN-2(T) and SH-4 represent a novel species of the genus Halorubrum, for which the name Halorubrum aquaticum sp. nov. is proposed. The type strain is EN-2(T) ( = CECT 7174(T)  = CGMCC 1.6377(T)  = JCM 14031(T)).

Structure of the gene coding for the alpha polypeptide chain of the human complement component C4b-binding protein.

The human gene coding for the 70-kD polypeptide of the complement regulatory component C4b-binding protein (C4BP alpha) spans over 40 kb of DNA and is composed of twelve exons. Upon transcription in liver, or in Hep-G2 cells, this gene produces a single transcript of 2,262 nucleotides, excepting the poly A tail, that presents an unusually long 5' untranslated region (5' UTR) of 223 nucleotides. The C4BP alpha gene is organized as follows: the first exon codes for the first 198 nucleotides of the 5' UTR. It is separated by a large intron from the second exon including the remaining of the 5' UTR and the coding region for the signal peptide. Each of the eight 60-amino acid repeats (short consensus repeats [SCRs]) that compose the C4BP alpha polypeptide chain is encoded by a single exon, except for the second SCR, which is split in two exons. At the 3' end of the C4BP alpha gene, the twelfth exon codes for the COOH-terminal 57 amino acids of the mature protein, which have no similarities to the SCRs, and the 245 nucleotides of the 3' UTR. Examination of the nucleotide sequence of the first exon revealed an interesting characteristic, strongly suggesting that this exon may specify a functional domain of the C4BP alpha transcript. It includes two in-phase ATG codons, in a different frame respect to that coding the C4BP alpha polypeptide, followed by an in-frame termination codon, also within the first exon. Comparison between mouse and human C4BP alpha transcripts indicates conservation of this structure within the 5' UTR. C4BP is expressed in the liver and is an acute phase protein. A computer search of the genomic sequences upstream the transcription start site demonstrates the presence of potential cis-acting regulatory elements similar to those found in the promoters of other liver-expressed and/or acute phase genes.

Successful renal transplantation in a patient with atypical hemolytic uremic syndrome carrying mutations in both factor I and MCP.

Kidney transplantation in patients with atypical hemolytic uremic syndrome (aHUS) carrying mutations in the soluble complement regulators factor H (CFH) or factor I (CFI) is associated with elevated risk of disease recurrence and almost certain graft loss. In contrast, recurrence is unusual in patients with mutations in the membrane-associated complement regulator membrane cofactor protein (MCP) (CD46). Therefore, a panel of experts recently recommended the combined liver-kidney transplantation to minimize aHUS recurrence in patients with mutations in CFH or CFI. There was, however, very limited information regarding transplantation in patients carrying mutations in both soluble and membrane-associated complement regulators to support a recommendation. Here, we report the case of an aHUS patient with a heterozygous mutation in both CFI and MCP who received an isolated kidney transplant expressing normal MCP levels. Critically, the patient suffered from a severe antibody-mediated rejection that was successfully treated with plasmapheresis and IvIgG. Most important, despite the complement activation in the allograft, there was no evidence of thrombotic microangiopathy, suggesting that the normal MCP levels in the grafted kidney were sufficient to prevent the aHUS recurrence. Our results suggest that isolated kidney transplantation may be a good first option for care in aHUS patients carrying CFI/MCP combined heterozygous mutations.

Bone modification of the college american football player: longitudinal study / Modificaciones óseas del jugador de futbol americano universitario: estudio longitudinal

The purpose of this study was to know the bone changes of college football (FA)players. A total of 39 male FA players participated, ranging in age from 18 to 25 years old. They were grouped according to each playing position they play in the team such as: Linemen (n = 15), players of great skills (n = 7), players of skill (n = 13) and quarterbacks (n = 4). For the assessment of BMD (g/cm2) a Double X-ray Bone Densitometry (DXA) was used. The results of this study showed a significant decrease (p<.05) of BMD in head and legs, in contrast, the CMO showed an increase in legs, however, in the pelvic region showed a significant decrease (p<.05). In conclusion, significant changes were found for BMD and CMO in the head, leg and pelvis regions in college AF players over a one-year span of competition (AU)

El propósito de este estudio fue conocer los cambios óseos de los jugadores de futbol americano (FA) universitario. Participaron un total de 39 jugadores de FA masculino, con rangos de edad de 18 a 25 años. Se agruparon acorde a cada posición de juego que desempeñan en el equipo como: Linieros (n=15), jugadores de grandes habilidades (n=7), jugadores de habilidad (n=13) y mariscales de campo (n=4). Para la valoración de DMO (g/cm2) se utilizó un Densitometría Ósea Doble de Rayos X (DXA). Los resultados de este estudio mostraron una disminución significativa (p<.05) de DMO en cabeza y piernas, en cambio, el CMO mostró un aumento en piernas, sin embargo, en la región de pelvis mostro una disminución significativa (p<.05). En conclusión, se encontraron cambios significativos para la DMO y CMO en las regiones de cabeza, piernas y pelvis en los jugadores de FA universitario en un lapso de un año de competencia (AU)

[PCSK-9 inhibitors, effects on LDL-C and future implications: What you should know]. / Inhibidores de PCSK-9, efectos sobre el cLDL e implicaciones futuras: lo que se debe saber.

The discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) in 2003 in families with familial hypercholesterolemia (HF) later generated the development of pharmacological strategies in order to inhibit this protein. Twelve years after this discovery, the first two biological compounds (monoclonal antibodies) were approved, which have been shown to substantially decrease LDL-C and other lipid subfractions. The objective of the present article is to review the history of the discovery of PCSK9, its physiology and pathophysiology and subsequent pharmacological development. The objectives and goals reached to date and the pending questions regarding the efficacy and safety of its clinical use are presented.

Proteolytic activity of the different fragments of factor B on the third component of complement (C3). Involvement of the N-terminal domain of Bb in magnesium binding.

Kinetic experiments measuring the proteolytic activity of Bb and 33Kd fragment (the C-terminal domain of factor B) on C3 were performed in several conditions, in order to assess the role of factor B domains in the catalytic activity and magnesium binding. The experiments were carried out in fluid phase with 125I-C3 or C3(H2O) as substrates and in the presence of nonradioactive C3b as cofactor. The results indicate: (a) The C-terminal domain, 33Kd, possesses proteolytic activity on C3, which is Mg2(+)-independent, whereas proteolysis by Bb is enhanced in 5 mM Mg2+. (b) C3b behaves as cofactor of 33Kd proteolytic activity on C3 and factor H is able to inhibit this activity. (d) Kinetics of C3 proteolysis by 33Kd shows a lag phase which is also displayed by Bb in the absence but not in the presence of Mg2+. Taken together these data are consistent with the involvement of the N-terminal domain of Bb in Mg2+ binding, which results in an enhancement of the proteolytic activity on C3 of the adjacent C-terminal domain. A C3 convertase model accounting for these results is presented.

The interaction of 1-anilino-8-naphthalene sulphonate with human C1q.

C1q has 12 binding sites for 1-anilino-8-naphthalene sulphonate (ANS), two per peripheral subunit. This number increases to 18 upon weak-acid-induced conformational transition in the globular heads. One ANS binding site is present in each C gamma 2 domain of human IgG. ANS is bound by C1q with a higher affinity (Ka = 2.07 X 10(6) M-1) than by the Fc fragment (Ka = 9.07 X 10(4) M-1) of human IgGl. Hence the inhibitory capacity of C1q binding to IgG immune complexes of ANS probably reflects its preferential binding to the globular heads of C1q. The characteristics of ANS-C1q binding may in part explain the hydrophobic component of the C1q-IgG interaction. It is suggested that an ionic-hydrophobic two-step process is involved in the contact between C1q and IgG.

Functional analysis in serum from atypical Hemolytic Uremic Syndrome patients reveals impaired protection of host cells associated with mutations in factor H.

A subgroup of patients with the most severe form of the Hemolytic Uremic Syndrome (HUS) presents mutations in the complement regulatory protein factor H. The functional analyses of the factor H mutant proteins purified from some of these patients have shown a specific defect in the capacity to control complement activation on cellular surfaces. Here, we show that these factor H-related complement regulatory defects can be detected in the patients' serum with a simple hemolytic assay. Data obtained from HUS patients and control individuals indicate that this assay is a useful tool for the molecular diagnosis of factor H-related HUS.

Separation of active and inactive forms of the third component of human complement, C3, by fast protein liquid chromatography (FPLC).

C3(H2O), an inactive form of C3 present to a variable extent in most C3 preparations, has been isolated in 40 min from previously purified C3 using FPLC ion exchange chromatography on a Mono Q column. As many as six peaks were obtained from some C3 preparations, corresponding to different molecular forms of the protein. One of these peaks consisted of a molecular form of C3 with intact alpha and beta chains, a free sulfhydryl group but no hemolytic activity and was identified as C3(H2O). C3(H2O) eluted as a homogeneous peak well resolved from native C3, C3b, high molecular weight aggregates and small degradation fragments. The same C3(H2O) peak was generated from native C3 by repeated freeze-thaw cycles or NH2OH treatment. C3(H2O) alpha chain appeared as a doublet about 2 kDa heavier than native C3 alpha chain in low cross-linked gels. Two forms of C3b could be separated on the Mono S column, both able to form the C3 convertase. The present report describes a very fast method to resolve and isolate to homogeneity C3(H2O) and native C3 from C3 preparations. Both molecular forms of C3 are very suitable for studies of the initial and amplification C3 convertases of the alternative pathway of complement.

Reduced cortisol potentiates the exercise-induced increase in corticotropin to a greater extent in trained compared with untrained men.

We examined the effect of acute exercise and reduced cortisol on pituitary and adrenal responsiveness and the impact of reduced plasma cortisol on maximal oxygen consumption (VO2max) in eight trained (T) and eight untrained (UT) males. Subjects completed two graded maximal exercise tests (GXT), each preceded by either overnight metyrapone (MET) or placebo (PLA) administration. Blood samples were collected before and after GXT. With PLA, resting corticotropin (ACTH) levels were higher in T versus UT men; however, cortisol and 11-deoxycortisol were similar between groups. Following GXT on PLA, cortisol was unchanged but 11-deoxycortisol increased in both groups; however, ACTH increased only in UT men. For both groups, cortisol, 11-deoxycortisol, and ACTH were different post-GXT with MET versus PLA. Furthermore, following GXT with MET, the ACTH response was greater in T versus UT subjects. VO2max was not altered by MET in either group. We conclude that (1) at rest, only ACTH levels differed between T and UT men; (2) individually, the GXT and MET provide a similar ACTH response in UT but not in T subjects; (3) when GXT and MET are superimposed, they provide a stronger stimulus to pituitary and adrenal reserve than either test alone; (4) the combination of MET and GXT elicits a greater ACTH response in T compared with UT men; and (5) an acute reduction in plasma cortisol does not alter VO2max.

Metabolic effects of low cortisol during exercise in humans.

This study examined the physiological effect of reduced plasma cortisol (C) during prolonged exercise in humans. The effects of normal C (NC) were compared with metyrapone-induced low C (LC) on plasma substrate availability and the respiratory exchange ratio during 2 h of exercise at approximately 60% peak O2 consumption in nine subjects. The C responses were compared with preexercise (Pre) levels and with a rest day (Con). At rest, C was attenuated by approximately 70% for LC compared with NC. At rest, plasma glucose, lactate, glycerol, beta-hydroxybutyrate, alanine, branched-chain amino acids, insulin, glucagon, growth hormone, epinephrine, and norepinephrine were similar under LC and NC (P > 0.05). During exercise under NC, plasma C increased compared with Pre, whereas it remained unchanged during LC. During NC, plasma C was elevated at 90 min (compared with Con) and at 120 min (compared with Con and Pre). During exercise, plasma glucose decreased to the same extent and lactate was similar under both conditions, whereas plasma glycerol, beta-hydroxybutyrate, alanine, and branched-chain amino acids were higher (P < 0.01) under NC. Plasma insulin declined (P = 0.01) to a greater extent under LC, whereas growth hormone, epinephrine, and norepinephrine tended to be higher (0.05

The effect of exercise on serum and salivary cortisol in male children.

The purpose of this study was to examine serum and salivary cortisol responses to cycling exercise in male children, 10.6 +/- 0.2 yr (mean +/- SE). Each child performed a graded exercise test on a cycle ergometer to determine VO2max. On a separate day, a 30-min bout of exercise at 70% of VO2max was performed. Blood, obtained from a venous catheter, and saliva samples were collected at rest, at 15 and 30 min of exercise, and 15 min post-exercise. The mean serum cortisol level at 15 min (7.94 +/- 1.43 micrograms.dl-1) and 30 min (8.72 +/- 1.77 micrograms.dl-1) of exercise and at 15 min post-exercise (8.21 +/- 1.59 micrograms.dl-1) were significantly greater than rest (5.54 +/- 0.86 micrograms.dl-1). The increase in salivary cortisol levels over time approached (P = 0.08), but did not reach significance. However, effect size analyses indicated that the increase in salivary cortisol at 30 min of exercise (0.64) and 15 min post-exercise (0.62) was similar to the change in serum cortisol at these same two time points (0.72 and 0.66, respectively). Serum and salivary cortisol were correlated (P < 0.05) at 15 min of exercise (r = 0.77), 30 min of exercise (r = 0.90), and 15 min post-exercise (r = 0.84), but not at rest (r = 0.46). In conclusion, 30 min of submaximal exercise at 70% of VO2max significantly increased serum cortisol level; and salivary and serum cortisol are correlated during and after exercise.

Blood lactate and perceived exertion relative to ventilatory threshold: boys versus men.

The purpose of this study was to examine blood lactate (BLa) levels and ratings of perceived exertion (RPE) in nine boys (10.5 +/- 0.7 yr) and nine men (25.3 +/- 2.0 yr) during exercise relative to ventilatory threshold (VT). VT and VO2max were determined during a graded exercise test on a cycle ergometer. On three additional days each subject exercised for 10 min at either 80, 100, or 120% of the VO2 at VT. Capillary BLa levels and RPE were assessed at minutes 5 and 10 of each trial. VO2max averaged 47.7 +/- 5.4 and 50.2 +/- 6.2 mL x g(-1) x min(-1) in the boys and men, respectively (P > 0.05). VT expressed as %VO2max was 67.2 +/- 3.5% in the boys and 67.3 +/- 4.9% in the men (P > 0.05). BLa levels ranged from 2.0 +/- 0.7 to 4.7 +/- 0.9 mmol x L(-1) in the boys and from 2.6 +/- 0.5 to 8.2 +/- 2.1 mmol x L(-1) in the men across the three intensities. Corresponding RPE values ranged from 11.2 +/- 1.8 to 16.2 +/- 2.2 in the boys and from 10.2 +/- 1.2 to 15.8 +/- 1.7 in the men. A group x time x intensity interaction (P < 0.05) indicated that BLa in the men increased more so across time and intensity. There were no significant group difference or interactions involving RPE during exercise. Setting exercise intensity relative to VT did not abolish child-adult differences with respect to submaximal BLa levels. Despite maintaining lower BLa levels, RPE values were similar between boys and men.

Psychological treatment of chronic posttraumatic stress disorder in victims of sexual aggression.

The aim of this research was to test the comparative effectiveness of two therapeutic modalities in the treatment of chronic posttraumatic stress disorder in victims of sexual aggression: (a) self-exposure and cognitive restructuring and (b) progressive relaxation training. The sample consisted of 20 patients (victims of rape in adulthood or adult victims of childhood sexual abuse) selected according to DSM-III-R criteria. A multigroup experimental design with repeated measures (pretreatment, posttreatment, and 1-, 3-, 6-, and 12-month follow-up) was used. Most treated patients improved, but the success rate was higher in all measures in the exposure and cognitive restructuring group immediately on posttreatment and at follow-up. Implications of this study for clinical practice and future research in this field are commented on.

[Intracranial venous thrombosis: a study of 16 cases and a review of the literature]. / Trombosis venosa intracraneal: estudio de 16 casos y revisión de la bibliografía.

INTRODUCTION: The clinical picture and aetiology of intracranial venous thrombosis are highly variable. Early descriptions reported it as a rare disease with a poor prognosis but the advent of neuroimaging techniques, and a deeper knowledge of the clinical picture, have shown it to have a higher frequency and a better prognosis. OBJECTIVE: To report the clinical and neuroimaging findings in patients diagnosed as having intracranial venous thrombosis in our department and review the state of the literature. PATIENTS AND METHODS: We reviewed all discharge reports from patients admitted to the neurology department of the Juan Canalejo Hospital between 1975 and 2000. Of these, we reviewed the medical records of those patients diagnosed as having intracranial venous thrombosis in order to obtain data relating to the clinical manifestations, complementary tests, etiological and topographical diagnosis, treatment and outcome. RESULTS: Diagnosis of intracranial venous thrombosis was made in 16 patients. The most common symptom was headache. The superior sagittal was the most frequently affected sinus. In almost all patients CT results led to the suspicion, and in some cases the confirmation, of the diagnosis. The most frequently found aetiology was oral contraceptive consumption. Outcome was generally good both with anticoagulation and symptomatic treatments. CONCLUSIONS: The most important difference between the present study and earlier reports is in the frequency of the different aetiologies. Our findings provide further evidence that intracranial venous thrombosis is not an infrequent disease and that the prognosis is generally good.