Expression and localization of Aquaporin 3 (AQP3) in folliculogenesis of ewes

The mRNA expression and localization of Aquaporin 3 (AQP3) were investigated in the ovarian follicles of ewes at different stages of development (primordial, primary, secondary, small, and large antral). The gene expression was quantified by qPCR, while the protein identification and localization were determined by Western blot and immunohistochemistry, respectively. Analysis revealed that AQP3 mRNA was detected only in the antral follicles, whereas the protein expression was detected in the oocyte and granulosa cells in all stages of follicular development. The latter observation suggests that the presence of AQP3 in follicles of all categories, especially in the antral follicles, provides novel insights on the mechanisms that regulate the flow of water between cells during the formation of antral follicles in sheep.     

Activation of 2′,5′-oligoadenylate synthetase and B-2 microglobulin in cancer patients treated with partially pure gamma interferon: Dependence of biological effect on administration route

Summary Partially pure immune (gamma) interferon (IFN-gamma) was administered to patients intramuscularly (IM), by rapid IV bolus, and by 6-h continuous infusion as part of a phase I clinical trial. The activity of 2,5-oligoadenylate synthetase (2,5 A) in peripheral blood cells and the concentration of beta-2 microglobulin (B-2M) in serum were monitored as indicators of interferon biological activity in vivo. Five patients received IFN-gamma by the IM route in doses ranging from 6.5×10⁵ to 9.6×10⁶ antiviral units daily. There was little induction either of serum B-2M or of 2,5A in peripheral blood cells. Eight patients received IFN-gamma by rapid (5 min) IV bolus infusion in doses ranging from 6.5×10⁵ to 54×10⁶ antiviral units daily. As with IM administration, there was little significant induction of 2,5A synthetase, but the concentration of B-2M was increased above pretherapy values in most patients. Eleven patients received IFN-gamma by 6-h infusion daily for 10 days at a dosage of 27×10⁶ units/day. In contrast to IM and IV bolus administration, 6-h infusion of IFN-gamma resulted in significant induction of both B-2M serum concentration and of 2,5A activity in all patients. The induction of 2,5A was highest on days 2 and 4 of therapy and decreased to pretherapy values by day 7. During the second 10-day course of the infusion study 2,5A activity was not induced until day 7 of therapy, and it decreased rapidly thereafter. These studies show clearly that consistent biological activity such as B-2M activation and specific intracellular biochemical events such as 2,5A induction may be optimally obtained by the administration of IFN-gamma by continuous IV infusion.The study reported in this paper was supported by a grant from the Interferon Foundation. Research was conducted, in part, by the James E. Lyon Foundation for Research, the John D. and Catherine T. MacArthur Foundation, and the Clayton Foundation for Research. Dr Jordan Gutterman is a Senior Clayton Foundation Investigator.     

Comparative study of MTA and other materials in retrofilling of pulpless dogs' teeth

This in vivo study compared the effect of mineral trioxide aggregate (MTA), IRM, Super EBA and ZOE in a puttylike consistency, used as retrofilling materials, in the healing process of periapical tissue of pulpless dogs' teeth submitted to a conventional retrofilling technique. Twenty-four premolars obtained from three dogs were used. At the first intervention, the animals were anesthetized, coronal access was obtained and pulpectomy was done. Root canals were kept open to the oral environment for 180 days to induce the formation of apical lesions. After surgical removal of the lesions with curettes, 2 mm of the apical root was cut out perpendicular to the long axis of the teeth, and root-end cavities were shaped with a low-speed round bur. The bone cavities were irrigated and dried, and the root-end cavities were filled with MTA, IRM, Super EBA and ZOE in a puttylike consistency. The bone cavities were passively filled with blood and flaps were sutured. The coronal access openings were cleaned and double-sealed with ZOE and amalgam. After 180 days, the animals were killed by anesthetic overdose, maxilla and mandible were removed and the pieces were processed for histomorphologic analysis. Data were evaluated blindly on the basis of several histopathologic events and the scores obtained were analyzed statistically using the Kruskal Wallis test. No significant differences were observed among MTA, Super EBA and IRM (p>0.05). However, ZOE had a significantly more negative influence on the apical healing (p<0.05). In conclusion, MTA, Super EBA and IRM had similar histopathologic effects among each other and better performance than ZOE used in a puttylike consistency. Furthermore, only MTA stimulated hard tissue deposition in direct contact with the retrofilling material, even when it was inserted under critical conditions.     

OSI-930: a novel selective inhibitor of Kit and kinase insert domain receptor tyrosine kinases with antitumor activity in mouse xenograft models

OSI-930 is a novel inhibitor of the receptor tyrosine kinases Kit and kinase insert domain receptor (KDR), which is currently being evaluated in clinical studies. OSI-930 selectively inhibits Kit and KDR with similar potency in intact cells and also inhibits these targets in vivo following oral dosing. We have investigated the relationships between the potency observed in cell-based assays in vitro, the plasma exposure levels achieved following oral dosing, the time course of target inhibition in vivo, and antitumor activity of OSI-930 in tumor xenograft models. In the mutant Kit-expressing HMC-1 xenograft model, prolonged inhibition of Kit was achieved at oral doses between 10 and 50 mg/kg and this dose range was associated with antitumor activity. Similarly, prolonged inhibition of wild-type Kit in the NCI-H526 xenograft model was observed at oral doses of 100 to 200 mg/kg, which was the dose level associated with significant antitumor activity in this model as well as in the majority of other xenograft models tested. The data suggest that antitumor activity of OSI-930 in mouse xenograft models is observed at dose levels that maintain a significant level of inhibition of the molecular targets of OSI-930 for a prolonged period. Furthermore, pharmacokinetic evaluation of the plasma exposure levels of OSI-930 at these effective dose levels provides an estimate of the target plasma concentrations that may be required to achieve prolonged inhibition of Kit and KDR in humans and which would therefore be expected to yield a therapeutic benefit in future clinical evaluations of OSI-930.     

Identification of proteins in the accessory sex gland fluid associated with fertility indexes of dairy bulls: a proteomic approach

We evaluated the expression of proteins in the accessory sex gland fluid (AGF) and their relationships with fertility indexes of dairy bulls. Fertility was normalized as the percentage point deviation of their nonreturn rates (PD) from the average fertility of all bulls from a given artificial insemination center. Services associated with each sire ranged from 269 to 77 321 and PD values from +7.7% to -18.1%. AGF, from 37 bulls, was obtained with an artificial vagina after cannulation of the vasa deferentia. Proteins from AGF were separated by 2-dimensional SDS-PAGE followed by staining with Coomassie blue and analysis of polypeptide maps using PDQuest software. Bulls were divided in groups based on PD values and the optical density of spots in the AGF gels used as independent variables to predict bull fertility. Proteins were identified by capillary liquid chromatography nanoelectrospray ionization tandem mass spectrometry (CapLC-MS/MS). An average of 52 +/- 5 spots was detected in the AGF gels, but there were no spots unique to groups of either high- (PD > or = 0) or low- (PD < 0) fertility sires. The former were neither less nor more homogeneous than the latter based on correlations of all matched spots between pairs of AGF maps. However, high fertility of dairy bulls was significantly associated with lower expression of 14-kDa spermadhesin Z13 isoforms and higher amounts of 55-kDa osteopontin and 58-kDa phospholipase A2 (PLA2) isoforms. The average intensity of 5 spots identified as BSP 30 kDa in the AGF gels had a quadratic association with fertility indexes (R2 = .18; P = .03). PD values of bulls were related (R2 = .56) to the quantity of spermadhesin, osteopontin, and BSP 30 kDa in the AGF polypeptide maps. Bull fertility was also determined by another equation (R2 = .53) with spermadhesin, BSP 30 kDa, and PLA2 as independent variables. We conclude that interactions among several proteins in accessory sex gland fluid explain a significant proportion of the variation in fertility scores of mature dairy sires.     

The Role of Nutritional Support for Cancer Patients in Palliative Care

The role of nutritional support for cancer patients in palliative care is still a controversial topic, in part because there is no consensus on the definition of a palliative care patient because of ambiguity in the common medical use of the adjective palliative. Nonetheless, guidelines recommend assessing nutritional deficiencies in all such patients because, regardless of whether they are still on anticancer treatments or not, malnutrition leads to low performance status, impaired quality of life (QoL), unplanned hospitalizations, and reduced survival. Because nutritional interventions tailored to individual needs may be beneficial, guidelines recommend that if oral food intake remains inadequate despite counseling and oral nutritional supplements, home enteral nutrition or, if this is not sufficient or feasible, home parenteral nutrition (supplemental or total) should be considered in suitable patients. The purpose of this narrative review is to identify in these cancer patients the area of overlapping between the two therapeutic approaches consisting of nutritional support and palliative care in light of the variables that determine its identification (guidelines, evidence, ethics, and law). However, nutritional support for cancer patients in palliative care may be more likely to contribute to improving their QoL when part of a comprehensive early palliative care approach.     

Maternal Supplementation with Cow’s Milk Naturally Enriched with PUFA Alters the Metabolism of Sows and the Fatty Acid Profile of the Offspring

The study aimed to evaluate the supplementation of gilts with cow’s milk naturally enriched with n-3 and n-6 polyunsaturated fatty acids (PUFA) on reproductive outcomes, and the serum biochemical and FA profile of swine females and their offspring. During 316 days, 30 gilts were distributed into three groups: (1) Control, fed a basal diet + milk from cows without oil; (2) n-3, fed a basal diet + milk from cows fed a diet enriched with linseed oil; (3) n-6, fed a basal diet + milk from cows fed a diet enriched with soybean oil. The gilts receiving the diets containing PUFA had higher serum urea and very-low-density lipoprotein levels and lower serum total protein and low-density lipoprotein levels compared to the Control group. Females supplemented with n-3 presented higher serum palmitic acid and γ-linolenic acid levels than those fed n-6. Piglets from the Control group were heavier at birth than those from females supplemented with enriched milk. The piglets from females receiving enriched milk had 140 g higher body weight from 1 to 21 days old compared to the Control group, and greater average daily weight gain from 7 to 14 days old. The serum eicosapentaenoic acid level of piglets fed n-3 was 69% higher than those fed n-6, which reduced the AA/EPA ratio. Gilts supplemented with PUFA-enriched cow’s milk showed changes in their serum palmitic and γ-linolenic acid levels, in addition to improved performance, EPA concentration and consequently reduced AA/EPA ratio in their piglets, demonstrating beneficial results for their progeny.     

Principles of Sustainable Healthy Diets in Worldwide Dietary Guidelines: Efforts So Far and Future Perspectives

Food choices and eating behaviours have a large impact on both human and planetary health. Recently, the Food and Agricultural Organisation (FAO) of the United Nations and the World Health Organisation have developed a list of 16 guiding principles to achieve sustainable healthy diets (SHDs). They proposed that development of food-based dietary guidelines (FBDGs) should be a core element in the implementation of these SHDs in each country. The objective of this review is to explore the degree of alignment of current FBDGs to these guiding principles. A total of 43 FBDGs, written or translated into English, were collected from the online repository developed by the FAO and were analysed for their adherence to each of the guiding principles. Results were stratified for period of publication and geographical macro-area. Overall, there were high levels of inclusion of the factors related to health outcomes, especially in the most recent FBDGs. Conversely, environmental impact and socio-cultural aspects of diet were considered less frequently, especially in the older FBDGs. These results highlight the importance of revising FBDGs, especially to include emerging topics which represent the areas with the highest scope for improvement in the future versions of FBDGs. Replication of the present study in the coming years will be worthwhile to monitor improvements in the adherence of global FBDGs to the guiding principles of SHDs. The attainment of such a goal could promote a more rapid transition towards SHDs, as well as highlighting pivotal research trajectories to increase adoption and evaluate the impact on the food system.     

Somatosensory control of precision grip during unpredictable pulling loads

Summary In the previous paper regarding the somatosensory control of the human precision grip, we concluded that the elicited automatic grip force adjustments are graded by the amplitude of the imposed loads when restraining an active object subjected to unpredictable pulling forces (Johansson et al. 1992a). Using the same subjects and apparatus, the present study examines the capacity to respond to imposed load forces applied at various rates. Grip and load forces (forces normal and tangential to the grip surfaces) and the position of the object in the pulling direction (distal) were recorded. Trapezoidal load force profiles with plateau amplitudes of 2 N were delivered at the following rates of loading and unloading in an unpredictable sequence: 2 N/s, 4 N/s or 8 N/s. In addition, trials with higher load rate (32 N/s) at a low amplitude (0.7 N) were intermingled. The latencies between the start of the loading and the onset of the grip force response increased with decreasing load force rate. They were 80±9ms, 108 ±13ms, 138 ± 27 ms and 174 ± 39 ms for the 32, 8, 4 and 2 N/s rates, respectively. These data suggested that the grip response was elicited after a given minimum latency once a load amplitude threshold was exceeded. The amplitude of the initial rapid increase of grip force (i.e., the catch-up response) was scaled by the rate of the load force, whereas its time course was similar for all load rates. This response was thus elicited as a unit, but its amplitude was graded by afferent information about the load rate arising very early during the loading. The scaling of the catch-up response was purposeful since it facilitated a rapid reconciliation of the ratio between the grip and load force to prevent slips. In that sense it apparently also compensated for the varying delays between the loading phase and the resultant grip force responses. However, modification of the catch-up response may occur during its course when the loading rate is altered prior to the grip force response or very early during the catch-up response itself. Hence, afferent information may be utilized continuously in updating the response although its motor expression may be confined to certain time contingencies. Moreover, this updating may take place after an extremely short latency (45–50 ms). Our findings support the idea that the initiation as well as ongoing regulation of the motor responses is dependent on supraspinal control, but afferent signals directly processed through fast segmental networks may also contribute in the regulation. The grip force responses to the unloading phases, they were also graded by the load force rate and the response latencies increased with decreasing load force rate. However, the latencies were longer and more variable, and no catch-up responses were observed. Rather, the grip force decline was programmed for the inter-trial grip force level.     

Nutritional evaluation of some processed catering foods

Five prepared catering dishes were analysed to evaluate the proximate composition and the fatty acids, vitamin E, thiamine and riboflavin content. The correspondent values were calculated from actually available food composition tables (two from Italy, one from the UK and one from the USA). When using more than one database to calculate the composition of a complex recipe the average values were similar to the analytical ones despite the wide range reported for some variables. However, there was no significant difference in the statistical analyses between the analytical values and databases, or among the databases themselves. Therefore if the composition of a specific recipe is required, analyses would be advisable, but the available databases are quite adequate if the evaluation is for groups of people, even allowing for the seasonal variability of ingredients.