[Gastrointestinal manifestations of cystic fibrosis in children]. / Manifestaciones gastrointestinales en fibrosis quística en una población pediátrica.

INTRODUCTION: Cystic fibrosis (CF) is a multisystemic disease, with high morbidity and mortality, and its early diag nosis improves results. Lung conditions are the main cause of morbidity and mortality and are clo sely related to nutritional status and survival. There is little national information about the liver and gastrointestinal characteristics in pediatric patients with CF. OBJECTIVE: to describe at a gastrointes tinal level, the general, nutritional, and genetic characteristics and the evolution of CF carriers with/ without neonatal screening. PATIENTS AND METHOD: Retrospective study carried out in 4 public referral hospitals in the Metropolitan Region. The diagnosis of CF confirmed with two positive sweat tests (Gibson and Cooke method) was considered as an inclusion criterion. Those patients with unconfir med neonatal screening tests through Immunoreactive Trypsinogen (IRT) or with only one positive sweat test were excluded. Sex, age, nutritional status, date of diagnosis, clinical presentation at the onset, evolution, and therapies received were recorded as clinical variables, and as laboratory ones, genetic study by means of a diagnostic panel with 36 mutations. The STATA 12 software was used for statistical analysis. RESULTS: 127 patients were included. Respiratory manifestations (recurrent obstructive bronchial syndrome and pneumonia) were present in >60% and gastrointestinal ones (mainly malabsorption and malnutrition syndrome) in >80% of patients. On average, diagnostic confirmation took 4 months. The diagnosis guided by IRT was associated with better nutritional outcomes in the evolution of the patient. In 81.1% of the patients, the genetic study was performed. The most frequent mutations were those associated with DF508 (deletion of phenylalanine 508). 5.8% of the patients presented mutations not included in the gene panel used. CONCLUSIONS: Gas trointestinal CF appears with pancreatic, intestinal, and hepatic pathology throughout life. Malnutri tion is a frequently present factor, which worsens the prognosis. The management of gastrointestinal manifestations and malnutrition are relevant to improve the morbidity and mortality of CF patients.

Investigation of seminal plasma chitotriosidase-1 and leukocyte elastase as potential markers for 'silent' inflammation of the reproductive tract of the infertile male - a pilot study.

Inflammatory mediators - chitotriosidase-1 (CHIT1) and leukocyte elastase (LE) - were analyzed in human seminal plasma in relation to total antioxidative status (TAS) and pro-inflammatory markers IL-1ß and IL-6. Samples collected from 34 males who were part of infertile couples were divided into normozoospermic (N; n = 12, without symptoms of inflammation), oligozoospermic (O; n = 11) and teratozoospermic (T; n = 11) groups. significant differences were observed only in CHIT1 concentration between N and O samples. However, a higher mean LE concentration was also observed in O and T patients (3.7-times and 900-times, respectively) compared with the N group. in IL-1ß and IL-6 concentrations, an upward trend was observed from N, through O, up to the T group. The positive correlation between the concentration of IL-1ß and the activity and specific activity of CHIT11 as well as the moderate negative correlation between concentrations of IL-1ß and CHIT1 may suggest that elevated CHIT11 levels appeared in early stages of inflammation before the increase in IL-1ß concentrations, or remained stable even after the levels of cytokine decreased. The above seem to confirm the role of CHIT1 in the manifestation of 'silent' inflammation at a very early stage. To conclude, CHIT1 concentration appears to be an interesting biomarker that signals the presence of possible 'silent' inflammation accompanying oligozoospermia. We cannot draw such conclusions regarding LE concentration, because, although we observed differences in the mean values and medians between analyzed groups, they were not significant. The utility of CHIT1 in the follow-up of oligozoospermia-associated 'silent' subclinical inflammation is promising, but further studies on a larger patient test set are required.

Comparing dopaminergic dynamics in the dorsolateral striatum between adolescent and adult rats: Effect of an acute dose of WIN55212-2.

During adolescence dopaminergic neurotransmission shows transient changes until reaching adulthood. The administration of CB1 agonists such as WIN55212-2 during adulthood increases dopamine extracellular levels. However, the effects of acute administration of cannabinoids on nigrostriatal dopamine neurotransmission during adolescence are not fully elucidated. The aim of this research is to compare dorsolateral striatum (DLS) dopamine (DA) dynamics and to study the effect of WIN55212-2 on DLS DA dynamics during adolescence and adulthood. No-net flux microdialysis experiments were carried out in adolescent (post-natal day 35-40) and young-adult (post-natal day 70-75) urethane-anesthetized rats. Basal DA dialysate, DA extraction fraction (Ed) and extracellular concentration of DA (Cext) in DLS were assessed after an acute injection of WIN55212-2 (1.2 mg/kg) or vehicle. An increased basal DA dialysate and DA Ed were observed during adolescence compared to adulthood. Moreover, WIN55212-2 increases DLS DA Cext rising basal DA dialysate in adulthood and decreasing DA Ed in adolescence. Our results suggest that an age-dependent mechanism underlies the effect of WIN 55212-2 on DA balance between release and uptake in DLS.

Evaluation of intra-testicular injections of calcium chloride and 4-vinylcyclohexene 1,2 monoepoxide for chemical sterilization in guinea pigs.

This study was aimed at investigating the use of intra-testicular calcium chloride (CaCl2) and 4-vinylcyclohexene 1,2-monoepoxide (VCM) injections as a side effect-free alternative method for the control of reproduction in guinea pigs. Fifty male guinea pigs were randomly assigned to five groups. In all groups, the chemical agents were injected into both testes in 1% lidocaine hydrochloride. While Groups I, II and III were administered with a single dose (0.25 mL) of sterile physiological saline, 15 mg/100 g CaCl2, and 240 mg/kg VCM, respectively, Group IV and V received a daily dose of 15 mg/100 g CaCl2, and 240 mg/kg VCM for 3 days, respectively. On day 90 post-administration, all animals were weighed and later decapitated under ether anaesthesia. Blood and tissue (testis, liver, hypophysis and adrenal gland) samples were taken. Sperm samples from the cauda epididymis were examined for spermatological parameters. Blood was used for hormone analyses and tissue samples were examined histopathologically (haematoxylin-eosin) and immunohistochemically (Tunel staining). The epididymal sperm count decreased in all treatment groups. Excluding 2 animals, Group V displayed azoospermia. When compared to the control group, Group V displayed the highest prolactin and lowest testosterone levels, and Group III showed the highest testosterone level. Histopathological examination revealed no intoxication finding. Chemical castration with VCM may be a good alternative to surgical castration as it enables mass sterilization without postoperative risks in guinea pig.

Adrenergic stimulation and blocking of hormonal secretion activity of cultured cow granulosa cells.

The aim of this study was to determine the influence of alpha- and beta-stimulators (alpha-stimulator: detomidinum HCl) as well as blockers (alpha1-blocker: doxazosin, alpha2-blocker: yohimbinum HCL, beta-blocker: carazolol) on bovine granulosa cells culture from preovulatory follicles. The cell culture was passed in TCM 199 medium with 10% FCS and antibiotics. Tested substances were added to the culture medium in different concentrations. The experiment began when at least 80% of the wells were covered (in four well culture dish of NUNCK-DK). The culture medium was collected every 24 h for hormone analysis. Hormone levels of T, E2, and P4 were determined. The culture was used up to 120 hours. Our results showed a decrease in P-4 secretion after detomidinum addition for all tested concentrations. A slight testosterone level increase was seen in the first 24 hours and then its concentration remained at a constant low level. A slight increase in 17-beta estradiol secretion was also observed. After yohimbinum addition, a statistically significant decrease of progesterone was observed for all concentrations tested. No significant changes were observed at other hormones levels when compared with the control. Doxazosin, when added into the culture medium, did not cause any statistically significant changes in hormone secretions. The addition of carazolol caused a significant decrease in progesterone secretion after culturing for 48 hours. Changes observed in other hormones levels did not differ statistically from the control. These results seem to support the hypothesis that drugs stimulating and blocking adrenergic receptors may play some role in ovarian steroidogenesis in cows.

The influence of alpha-adrenergic receptors stimulator and blockers and beta-blocker on the ovary and endocrinological activity in heifers during superovulation.

Twenty five Holstein-Friesian heifers, clinically normal and with regular oestrous cycles, were used for induction of superovulation (PMSG-PGF(2)alpha-Neutra-PMSG). Animals were divided into 5 groups receiving: I - detomidine (40 microg/kg b.w.), II - doxazosin (0.2 mg/kg b.w.), III - yohimbine HCL 1% (1 ml/50 kg b.w.), IV - carazolol (0.01 mg/ kg b.w., i.v.), and V - physiological saline (1 ml/50 kg b.w.). The heifers with PGF2 alpha-induced cycles were treated with the substances 88 hrs after being given a single i.m. injection of 2500 IU PMSG. All animals were examined by ultrasonography, and by the number and size of ovarian follicles > 3 mm in diameter. The follicles were divided into 3 groups according to the diameter. Blood plasma was stored at -20 degrees C until LH, P4, E2 and PGFM analyses. In the control (V) group, two waves of follicle growth were observed. Yohimbine produced a significant blockage of ovulation. The mean number of corpora lutea in the group III was significantly lower than that in the control group (p< 0.02). No significant differences in the number of corpora lutea were observed between the groups I, II and III. The increase in E2 concentrations could be the response to the PMSG treatment with two waves of growth of large follicles before and after ovulation. Pulsatile LH release was altered by yohimbinum injection, however, the greater amplitude of pulses immediately following yohimbinum administration are suggestive of a positive influence of the alpha-2 adrenergic receptors antagonist. Yohimbinum administration did not affect plasma concentration of examined hormones. There was a difference between the plasma levels of LH after the doxazosin injection. Single injection of the stimulators and blockers of adrenergic receptors did not affect superovulatory response in terms of the numbers of CL, unruptured follicles and embryos recovered. The affectivity of artificial insemination was not significantly different between the control group and the detomidinum groups, while in the yohimbinum group it was significantly lower.

[Sperm, LH FSH, testosterone evaluation in patients with testicular cancer. Preliminary study]. / Ocena wybranych parametrów nasienia i poziomów hormonów FSH, LH, testosteronu u chorych na raka jadra. Doniesienie wstepne.

In the last 20 years the treatment results of testicular cancer has been improved. At the present time up to 90% of patients are cured. Following successful treatment young men want to assess their fertility and possibility to have children. 18 men with testicular cancer has been treated in Institute of Oncology in Warsaw. Before and/or after orchidectomy semen analysis and assessment of serum levels of FSH, LH, testosterone has been performed. The quality of the semen is much worse in the group with cancer compared to healthy controls. Semen analysis following orchidectomy revealed that spermatozoa count did not change, FSH, LH levels increased and testosterone level decreased.

Antimalarial activity: the search for marine-derived natural products with selective antimalarial activity.

In this short review, an approach to the isolation of potential antimalarial agents and lead compounds is outlined. A discussion of organism collection, followed by a description of biological testing and isolation methodologies, is also given. For two organisms, details of their secondary metabolite chemistry are reported. From one of these, Laurencia papillosa, the two aromatic compounds p-hydroxybenzaldehyde (1) and p-methoxybenzyl alcohol (2) were isolated. From the other, the tropical marine sponge Cymbastela hooperi, 15 diterpenes (3-17), which contain isonitrile, isothiocyanate, and isocyanate functionalities, are reported. Together with the diterpenes, three sesquiterpene hydrocarbons, 18-20, and the thiol, 21, were obtained. All structures were established by spectroscopic methods, particularly 1H-1H and 1H-13C shift-correlated 2D NMR spectroscopy and accurate mass measurement (HREIMS). The majority of isolates demonstrate significant and selective in vitro antimalarial activity. For compounds 4-17 a brief description of their possible structure-activity relationships is provided.

The effect of persistent chlorinated hydrocarbons on the secretion of estradiol and progesterone by bovine granulosa cells in vitro.

The role of persistent chlorinated hydrocarbons (PCH) in the reproductive disorders in ruminants is not well documented. In the present study we have examined the effect of these compounds and their metabolites on the secretion of estradiol (E2) and progesterone (P4) by bovine granulosa cells in vitro. Granulosa cells were isolated from large follicles (> or = 8 mm diameter) by gently washing the internal follicle wall. Aliquots of approximately 4 X 10(5) viable granulosa cells in 0.5 ml medium were cultured at 37 degrees C in an atmosphere of 5% CO2 and 95% air. Granulosa cells were cultured for 96h in a medium containing different concentrations (10(-1)-10(-4) ng/ml) of a PCH combination. Estradiol and progesterone were measured in unextracted granulosa cell culture medium by Enzyme Immunoassay (EIA). The exposure of granulosa cells to a combination of these organochlorine compounds in vitro results in a slight decrease of estradiol secretion only at the highest studied concentration of the PCH combination. However, the secretion of progesterone by these cells was seriously decreased, even by concentrations found in ovaries from animals kept under natural environmental conditions. The in vitro culture system of granulosa cells from preovulatory follicles may be useful in screening toxic effects of pesticides in animal reproduction.

Characteristics and analysis of uterine electromyographic activity in pregnant cows.

The electromyographic activity of the cow uterus in the last trimester of pregnancy was investigated. The investigation was performed on 12 animals and the electrical activity was recorded in the last trimester of pregnancy during 11 different periods until the delivery. The duration of the action potential bursts (APB) recorded during the first 7 periods, was small. It did not exceed 2 seconds. A significant increase, however, was recorded at 7 to 9 days before the labor and it involved all the investigated areas in the uterus. The number of APB of the gravid horn was significantly higher than that recorded at other locations in the uterus with the exception of the day of delivery. A significant correlation was found between the number of APB and the level of magnesium in blood serum. The levels of 17-beta estradiol and progesterone were similar during all studied periods with the exception of the last week, in which a dramatic fall in estradiol level and a significant increase in the progesterone concentration were observed. The results showed that it is possible to distinguish three different phases of electric activity in the cow uterus during the last trimester of pregnancy. The features of these phases were discussed.

[Effect of the action of stimulants and blockers of adrenergic receptors on the electrical activity of the uterus in pregnant cows]. / Efecto de la acción de estimulantes y bloqueadores de los receptores adrenérgicos sobre la actividad eléctrica del utero en vacas preñadas.

The effects of stimulants and inhibitors of adrenergic receptors on the myoelectric activity were studied in pregnant cows at different points of the last trimester of pregnancy. The results showed that noradrenaline produced an increase of the myoelectric activity of the uterus specially at the 6th week before parturition. Furthermore i.v. infusion of propranolol potentiated and of phentolamine diminished the stimulating activity of noradrenaline.

Tubular adaptation to Pi restriction in hypophysectomized rats.

The renal tubule adapts its tubular transport capacity for inorganic phosphate (Pi) in response to a reduction in the Pi supply. In order to assess whether growth hormone plays a critical role in this adaptive response we have studied the change in the tubular handling of Pi which follows Pi restriction in hypophysectomized (HPX) rats and compared it to that occurring in intact counterparts. HPX and intact rats were maintained either on a 1.2 g/100 g phosphorus diet or fed a 0.2 g/100 g phosphorus diet for 3, 6 or 12 days. HPX rats received ACTH and thyroxine in doses which normalize their low glomerular filtration rate (GFR). Then the maximal net Pi reabsorption per volume of glomerular filtrate (max. TRPi/ml GFR) were determined during acute Pi infusion by clearance technique. The results indicate that HPX rats responded to Pi restriction by raising their tubular capacity to reabsorb Pi. However, the rapidity and the magnitude of the adaptive response was significantly less in HPX than in intact rats. The adaptation to Pi restriction was also observed in HPX rats after thyroparathyroidectomy. It is concluded that growth hormone and other pituitary hormones do not play a key role in the adaptive response to Pi restriction. The reduced adaptive response observed in HPX rats with intact thyroparathyroid glands could be due to the decreased Pi demand consecutive to impaired growth.