What is the source of free radicals causing hemolysis in stored blood?

The quality of stored blood can be deteriorated by hemolysis caused by free radicals. The purpose of this study was to elucidate whether neutrophile leukocytes are the source of free radicals in stored blood as in hemodialyzed patients. Resuspensions with low (LL) or high (HL) leukocyte concentrations were prepared from samples of twenty healthy volunteers. The samples were incubated for 10 days at 4 degrees C and then for one day at 37 degrees C. Markers of hemolysis and free radical metabolism were examined before and after incubation in LL and HL samples. In spite of the difference of leukocytes counts in LL and HL resuspensions (p<0.0001), the pre-incubation values of all laboratory parameters were practically identical. In post-storage samples, superoxide dismutase and glutathione peroxidase activities did not differ in either group. Reduced glutathione in erythrocytes and extracellular antioxidant capacity were insignificantly lower in HL resuspensions, but the increase of malondialdehyde was much more pronounced in the HL samples (p<0.0001). The degree of hemolysis, expressed as the extracellular increase of potassium (p<0.001), hemoglobin (p<0.05) and lactate dehydrogenase (p<0.05), was higher in the HL samples. Our results support the hypothesis that leukocytes participate in free radical production in stored blood.     

Roles of insulin-like growth factor Ⅱ in regulating female reproductive physiology

The number of growth factors involved in female fertility has been extensively studied, but reluctance to add essential growth factors in culture media has limited progress in optimizing embryonic growth and implantation outcomes, a situation that has ultimately led to reduced pregnancy outcomes. Insulin-like growth factor Ⅱ(IGF-Ⅱ) is the most intricately regulated of all known reproduction-related growth factors characterized to date, and is perhaps the predominant growth factor in human ovarian follicles. This review aims to concisely summarize what is known about the role of IGF-Ⅱ in follicular development, oocyte maturation, embryonic development, implantation success, placentation, fetal growth, and in reducing placental cell apoptosis, as well as present strategies that use growth factors in culture systems to improve the developmental potential of oocytes and embryos in different species. Synthesizing the present knowledge about the physiological roles of IGF-Ⅱ in follicular development, oocyte maturation, and early embryonic development should, on the one hand, deepen our overall understanding of the potential beneficial effects of growth factors in female reproduction and on the other hand support development(optimization) of improved outcomes for assisted reproductive technologies.     

Pesticide exposure: the hormonal function of the female reproductive system disrupted?

Some pesticides may interfere with the female hormonal function, which may lead to negative effects on the reproductive system through disruption of the hormonal balance necessary for proper functioning. Previous studies primarily focused on interference with the estrogen and/or androgen receptor, but the hormonal function may be disrupted in many more ways through pesticide exposure. The aim of this review is to give an overview of the various ways in which pesticides may disrupt the hormonal function of the female reproductive system and in particular the ovarian cycle. Disruption can occur in all stages of hormonal regulation: 1. hormone synthesis; 2. hormone release and storage; 3. hormone transport and clearance; 4. hormone receptor recognition and binding; 5. hormone postreceptor activation; 6. the thyroid function; and 7. the central nervous system. These mechanisms are described for effects of pesticide exposure in vitro and on experimental animals in vivo. For the latter, potential effects of endocrine disrupting pesticides on the female reproductive system, i.e. modulation of hormone concentrations, ovarian cycle irregularities, and impaired fertility, are also reviewed. In epidemiological studies, exposure to pesticides has been associated with menstrual cycle disturbances, reduced fertility, prolonged time-to-pregnancy, spontaneous abortion, stillbirths, and developmental defects, which may or may not be due to disruption of the female hormonal function. Because pesticides comprise a large number of distinct substances with dissimilar structures and diverse toxicity, it is most likely that several of the above-mentioned mechanisms are involved in the pathophysiological pathways explaining the role of pesticide exposure in ovarian cycle disturbances, ultimately leading to fertility problems and other reproductive effects. In future research, information on the ways in which pesticides may disrupt the hormonal function as described in this review, can be used to generate specific hypotheses for studies on the effects of pesticides on the ovarian cycle, both in toxicological and epidemiological settings.     

How can we improve tracking of transplanted tissue in the United States?

Currently an estimated two million tissues are distributed for transplantation annually. With increasing use of recovered tissue, clusters of transplant-transmitted infection have shown the difficulty of tracking tissues from an infected donor to the recipient. The challenge of tissue tracking to multiple transplant recipients was illustrated in a recent investigation of transmission of hepatitis C virus infection from a donor of organs and tissues. When a tissue bank issued a recall of the donated tissue, the Centers for Disease Control and Prevention was notified to assist public health authorities; the mean time to locate and notify the physicians who had transplanted the tissue was 13 days, while the mean time to notify, inform, and test the patients was 29 days. Lack of common coding and nomenclature was one of the key challenges in tracking tissue to the recipient. Some changes that could improve timeliness in the event of a recall includes: (1) standardized tissue nomenclature and coding through unique donor identifiers; (2) tissue traceability requirements using systems similar to that used for blood products; (3) a surveillance system for adverse events that provides feedback at the provider level.     

Male–female relatedness and patterns of male reproductive investment in guppies

Inbreeding can cause reductions in fitness, driving the evolution of pre- and postcopulatory inbreeding avoidance mechanisms. There is now considerable evidence for such processes in females, but few studies have focused on males, particularly in the context of postcopulatory inbreeding avoidance. Here, we address this topic by exposing male guppies (Poecilia reticulata) to either full-sibling or unrelated females and determining whether they adjust investment in courtship and ejaculates. Our results revealed that males reduce their courtship but concomitantly exhibit short-term increases in ejaculate quality when paired with siblings. In conjunction with prior work reporting cryptic female preferences for unrelated sperm, our present findings reveal possible sexually antagonistic counter-adaptations that may offset postcopulatory inbreeding avoidance by females.     

Could the egg itself be the source of the oviposition deterrent marker in the ectoparasitoid Dinarmus basalis?

Females of Dinarmus basalis, a solitary ectoparasitoid, strongly avoid superparasitising hosts bearing eggs which are 20 or more hours old. Our objective was to determine the mechanism by which the factors inducing host discrimination and such an oviposition deterring effect act, and the origin of the deterrent. This study showed that the information is carried by the parasitised host. It is acquired by a transfer of molecules from the wasp egg onto the host and it requires contact between egg and host for at least 4 h. The factors transferred do not, as commonly reported in other species, come from the female's genital apparatus but from the live egg itself. Consequently, the D. basalis egg directly participates in the success of parasitism by releasing factors which elicit the oviposition host deterring effect. The originality and the ecological importance of these results are discussed.     

Can the effect of soft tissue artifact be eliminated in upper-arm internal-external rotation?

The purpose of this study was to quantify the effect of soft tissue artifact during three-dimensional motion capture and assess the effectiveness of an optimization method to reduce this effect. Four subjects were captured performing upper-arm internal-external rotation with retro-reflective marker sets attached to their upper extremities. A mechanical arm, with the same marker set attached, replicated the tasks human subjects performed. Artificial sinusoidal noise was then added to the recorded mechanical arm data to simulate soft tissue artifact. All data were processed by an optimization model. The result from both human and mechanical arm kinematic data demonstrates that soft tissue artifact can be reduced by an optimization model, although this error cannot be successfully eliminated. The soft tissue artifact from human subjects and the simulated soft tissue artifact from artificial sinusoidal noise were demonstrated to be considerably different. It was therefore concluded that the kinematic noise caused by skin movement artifact during upper-arm internal-external rotation does not follow a sinusoidal pattern and cannot be effectively eliminated by an optimization model.     

Is accelerated oxidation of lactate required for dichloroacetate to lower the level of lactate in blood?

We examined mechanisms by which dichloroacetate (DCA), an activator of pyruvate dehydrogenase (PDH), led to a decrease in the concentration of lactate in blood in a unique "metabolic setting," where the concentration of lactate in blood was 5.4 +/- 0.5 mmol/L. Elevated levels of lactate were induced in anaesthetized rabbits by the administration of a large dose of insulin. The rate of consumption of oxygen was 1.2 +/- 0.1 mmol/min, the respiratory quotient was close to unity, and close to half of the PDH was in its active form; therefore, virtually all ATP synthesis should require flux through PDH. Hence, we predicted that DCA should not cause a significant decrease in the concentration of lactate in blood in this model. In contrast, if DCA was effective, new insights could be obtained into its mechanisms of action, at least in this setting. During steady-state hyperlactatemia, DCA was given as its sodium salt, 2 mmol/kg (n = 10); a control group (n = 5) received equimolar NaCl. Forty minutes later, the level of lactate in blood in the DCA group was 1.3 +/- 0.2 mmol/L, significantly lower than in the NaCl group (4.2 +/- 0.6 mmol/L). To determine the organ(s) responsible for removing lactate, arteriovenous differences were measured in organs drained by the jugular, femoral, and hepatic veins. There was no net uptake of lactate in these drainage beds after DCA was administered. From a quantitative analysis of the rate of removal of lactate and the rate of consumption of oxygen, it seems unlikely that the majority of the decrease in lactate could be directly attributed to an increase in its oxidation.     

Blood will tell (won't it?): A century of molecular discourse in anthropological systematics

Being derived from the hereditary material, molecular genetic data are often assumed to be a source of sounder inferences about evolution than data from other kinds of investigations. This, however, tends to be taken in the absence of a clear knowledge of the evolutionary processes at work, the technical shortcomings, and the manner of deriving the specific conclusions. The history of biological anthropology shows that, from the beginning of the 20th century, grossly naive conclusions have been promoted simply on the basis that they are derived from genetics, without having been fully thought-out. A balanced consideration of the shortcomings as well as the advantages of genetic data are necessary for its proper integration into the field. When molecular and morphological data disagree, both must be reexamined carefully, for genetics has been used irresponsibly as a form of scientific validation, both in American society and in American science. Contemporary data bearing on the molecular relationships of the apes are noteworthy for their diversity in quality, and need to be evaluated in the light of molecular and microevolutionary theory. © 1994 Wiley-Liss, Inc.     

Food and water consumption and the reproductive performance of the heat—acclimated female rat

Food and water consumption, estrus cycle length and regularity, mating rate, number of corpora lutea and morulae and early blastocytes on day 4 of pregnancy, were studied in a group of heat-acclimated female rats (35 ± 1°C). The results were compared with those of rats maintained at control temperature (22 ± 2°C). The heat-acclimated animals consumed the same quantity of food per 100 g of body weight as the controls. Water consumption in the heat was higher. Duration of estrus cycle was prolonged by 24% (p < 0.001), while the number of days associated with proestrus and estrus smears during the experimental period was smaller by 14% and 20% (p < 0.001), respectively. The number of days associated with metestrus and diestrus smears was larger by 25% and 24% (p < 0.001) respectively, in the heat-acclimated group as compared with controls. Mating rate was 47% lower (p < 0.01) in the 35°C group. There was no difference between the two groups in the number of corpora lutea, although the number of 4-day old morulae and early blastocysts in the heat-acclimated rats was 25% smaller (p < 0.01) than that of the control animals.

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Zusammenfassung Der Futter- und Wasserkonsum, die Länge und Regelmässigkeit des Oestruszyklus, die Aufnahmerate, die Anzahl Corpora Lutea und Blastozysten am 4. Trächtigkeitstage wurden in einer Gruppe Ratten bestimmt, die mehrere Wochen bei 35 ± 1°C gehalten worden waren. Die Kontrolltiere lebten bei 22 ± 2°C. In der Hitze war das Wachstum verzögert, der relative Futterkonsum (g/100 g Kp. Gew.) war aber bei beiden Gruppen gleich. Der Wasserkonsum war erhöht. Ebenso war der Oestruszyklus um 24% verlängert (p < 0,001). Während die Anzahl Tage mit Prooestrus and Oestrus um 14% bzw. 20% vermindert war, waren die mit Metoestrus und Dioestrus Zeichen vermehrt (p < 0,001). Die Anzahl Corpora Lutea war in beiden Gruppen gleich, dagegen war die Anzahl Blastozysten bei den Hitze-Ratten 25% geringer als bei den Kontrollen.

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Resume Des femelles de rats ont été acclimatées à la chaleur (35 ± 1°C). On a ensuite contrôlé leur consommation en eau et en nourriture, la longueur et la régularité de leur cycle menstruel, leur taux d'assimilation ainsi que le nombre de corpora lutea, de morulae et de blastocystes au 4ème jour de gestation. Les chiffres ainsi obtenus ont été comparés à ceux de rats maintenus à une température de contrôle (22 ± 2°C). Les rats acclimatés au chaud ont consommé autant de nourriture par 100 g de poids que ceux utilisés pour le contrôle. Il ont par contre bu davantage. La durée du cycle ovarien a été allongé de 24% (p < 0,001) alors que le nombre de jours avec proestrus et estrus a été réduit de 14%, respectivement de 20% et ceux présentant des signes de metestrus et diestrus a augmenté de 25 et 24% (p < 0,001). Le taux d'assimilation du premier groupe a diminué de 47% (p < 0,01) par rapport au second. On n'a pas constaté de différence en ce qui concerne le nombre de corpora lutea. Par contre le nombre de morulae et de blastocystes de 4 jours a été de 25% (p < 0,01) inférieur chez les rats acclimatés à celui des rats de contrôle.

     

Mapping histological levels of 8-hydroxy-2′-deoxyguanosine in female reproductive organs

Oxidative stress is associated with many disease states including gynecologic disease. This process can damage lipids, proteins and DNA. The present study highlights the role of oxidative stress induced DNA damage as measured by 8-hydroxy-2-deoxyguanosine in development of benign gynecological conditions (BGC). Our aim was to map the oxidative DNA damage on female reproductive organs and highlight the high amount found in a variety of benign gynecologic disorders. Seventeen biopsy specimens from female pelvic organs were divided in two groups: healthy organs tissue and BGC tissue. Healthy organs biopsy tissue included the cervix, tubes, uterus, peritoneum, and topic endometrium in secretory phase. Benign gynecological biopsy tissue included hydrosalpinges, leiomyoma, adenomyosis and tubal cysts. Immunohistochemical staining showed significantly higher levels of DNA damage between BGC and healthy organs [19.36 % (6.20; 32.51) vs. 4.61 % (0.63; 8.53); P < 0.0344]. Our results highlight the involvement of oxidative stress DNA damage in female benign pelvic disease. Hydrosalpinges, leiomyoma, and adenomyosis exhibit the highest amounts of oxidative DNA damage in the pelvic cavity.     

Could leptin be responsible for the reproductive dysfunction in obese men?

Low sperm concentration, increased fraction of morphologically abnormal sperm, and raised levels of markers of oxidative stress are often reported in the seminal plasma of infertile obese males. The precise reason for changes remains unknown. This short review summarises evidence from human and animal studies linking leptin to the reproductive dysfunction reported in obese males and presents a possible mechanism for this based on the available data in the literature. Serum leptin concentrations correlate positively with body fat mass but its precise link to semen abnormalities reported in obese males has yet to be conclusively established. Decreased sperm concentration, increased fraction of morphologically abnormal sperm and increased markers of oxidative stress have been reported following six weeks of daily leptin treatment to normal weight rats. In addition, decreased expression of endogenous antioxidant enzymes and increased expression of respiratory chain enzymes noted in the testes of leptin treated rats increases the propensity to oxidative stress. Besides that, leptin’s interference with histone to protamine transition in the DNA of sperm increases the susceptibility of sperm to free radical attack and may explain the often reported higher DNA fragmentation index in sperm of obese males. Concurrent supplementation of melatonin, a natural anti-oxidant, to these rats prevents the effects of leptin. The role of leptin in obesity-related reproductive dysfunction has to be considered seriously and these effects of leptin might involve increased oxidative stress.     

How well can blood pressure be controlled? Progress report on the Systolic Hypertension in Europe Follow-Up Study (Syst-Eur 2)

Background

The randomised, double-blind, placebo-controlled Systolic Hypertension in Europe trial (Syst-Eur 1) proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in elderly patients with isolated systolic hypertension. In an attempt to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine, the Syst-Eur patients remained in open follow-up after the end of Syst-Eur 1. This paper presents the second progress report of this follow-up study (Syst-Eur 2). It describes BP control and adherence to study medications.

Methods

After the end of Syst-Eur 1 all patients, treated either actively or with placebo, were invited either to continue or to start antihypertensive treatment with the same drugs as previously used in the active treatment arm. In order to reach the target BP (sitting SBP <150 mmHg), the first line agent, nitrendipine, could be associated with enalapril and/or hydrochlorothiazide.

Results

Of the 3787 eligible patients, 3516 (93%) entered Syst-Eur 2. At the last available visit, 72% of the patients were taking nitrendipine. SBP/DBP at entry in Syst-Eur 2 averaged 160/83 mmHg in the former placebo group and 151/80 mmHg in the former active-treatment group. At the last follow-up visit SBP/DBP in the patients previously randomised to placebo or active treatment had decreased by 16/5 mmHg and 7/5 mmHg, respectively. The target BP was reached by 74% of the patients.

Conclusion

Substantial reductions in systolic BP may be achieved in older patients with isolated systolic hypertension with a treatment strategy starting with the dihydropyridine calcium-channel blocker, nitrendipine, with the possible addition of enalapril and/or hydrochlorothiazide.