Long-term behavioral and morphological consequences of nonconvulsive status epilepticus in rats

The aims of the present study were to ascertain whether nonconvulsive status epilepticus (NCSE) could give rise to long-term behavioral deficits and permanent brain damage. Two months after NCSE was elicited with pilocarpine (15 mg/kg i.p.) in LiCl-pretreated adult male rats, animals were assigned to either behavioral (spontaneous behavior, social interaction, elevated plus-maze, rotorod, and bar-holding tests) or EEG studies. Another group of animals was sacrificed and their brains were processed for Nissl and Timm staining as well as for parvalbumin and calbindin immunohistochemistry. Behavioral analysis revealed motor deficits (shorter latencies to fall from rotorod as well as from bar) and disturbances in the social behavior of experimental animals (decreased interest in juvenile conspecific). EEGs showed no apparent abnormalities. Quantification of immunohistochemically stained sections revealed decreased amounts of parvalbumin- and calbindin-immunoreactive neurons in the motor cortex and of parvalbumin-positive neurons in the dentate gyrus. Despite relatively inconspicuous manifestations, NCSE may represent a risk for long-term deficits.     

Effects of carrier solution on insulin bioavailability

BACKGROUND: The aim of our study is to assess the influence of the base solution on the availability of biologic insulin expressed in the value of total insulin using the radioimmunoassay method and to monitor the influence of the base solution on the total insulin concentration over time. METHODS: Total insulin in a saline and in a total nutrient admixture was measured using the RIA method. In 15 experiments, the application of the saline by a perfusor (8 IU Actrapid HM, 100 IU/1 mL + 20 mL saline) was carried out at time intervals of baseline, 5, 10, 30, 60, 90, and 210 minutes. The application of the total nutrient admixture (8 IU Actrapid HM + 20 mL total nutrient admixture) was carried out in the same way. The MANOVA, ANOVA and paired t test with Bonferroni correction were then used for statistical evaluation. RESULTS: The average values of insulin concentration in saline at given time intervals were 21.5 +/- 11.3 mIU/L (5.4% of the theoretically calculated concentration). The level of insulin in the total nutrient admixture did not change over time, and it reached the values of 115.2 +/- 22.3 (28.8% of the theoretically calculated concentration). Changes in insulin concentration in time were found only in the saline (ANOVA time effect p < .001 for saline; p = .26 for total nutrient admixture). CONCLUSIONS: The availability of insulin was significantly higher in the total nutrient admixture solution than in the saline in the 3.5-hour experiment. The dependence of insulin concentration on time is present only in saline, and the main changes in insulin bioavailability are within first 60 minutes. The difference could be caused by smaller insulin absorption to the syringe walls and to the set, owing to the amino acids in the mixture. The question whether the amino acid concentration affects insulin bioavailability stays opened to other studies.     

Laparoscopic surgery in women with endometrial cancer: the learning curve

OBJECTIVE: The aim of this study was to assess the effect of increasing surgeons's experience in the laparoscopic surgery of women with endometrial cancer (EC) on the surgical outcome of these patients. STUDY DESIGN: Data were obtained from a prospectively collected database of 108 patients two oncolaparoscopic centers in Czech Republic who underwent laparoscopically assisted surgical staging (LASS) from April 1996 to March 2001. Patients were arranged in chronological order and divided into three groups, based on the date of their surgery. The three groups were compared in patient characteristics and surgical outcome using one-way analysis of variance (ANOVA) and Wilcoxon rank sum test. SETTING: Department of Obstetrics and Gynecology, Endoscopic Training Center, Baby Friendly Hospital Kladno, Czech Republic. RESULTS: The three groups were similar in patient characteristics. Operative times for laparoscopic staging with pelvic lymphadenectomy (LN) decreased significantly from mean of 156.3 min for group 1 to 142.8 min for group 3 (P < 0.05). In cases LASS with pelvic lymphadenectomy was significant increase in the number lymph nodes harvested (12.4 for group 1, 13.9 for group 2, and 15.4 for group 3, P < 0.05). In cases LASS without lymphadenectomy was not significant difference in operating time, estimated blood loss, rate of conversion to laparotomy, operative complications, and length of hospital stay among the compared groups. The number of patients who underwent para-aortic lymphadanectomy was too small (n = 22), and their distribution was asymmetrical for comparison. CONCLUSION: A learning curve is demonstrated in the LASS of women with endometrial cancer. With increasing surgeon's team experience, there is significant decrease in operative time for staging with pelvic lymph node dissection and increase in the number of pelvic lymph nodes removed. The para-aortic lymphadenectomy (PALN) was found to be more challenging than pelvic lymphadenectomy.     

Erythropoietin stimulates vasculogenesis in neonatal rat mesenteric microvascular endothelial cells

Human breast milk is a rich source of growth factors, including erythropoietin (Epo), the endogenous hormonal stimulant of erythropoiesis. Recombinant human Epo (rhEpo) has been shown to stimulate 1) angiogenesis, the process of new blood vessel growth from preexisting vessels; 2) vasculogenesis, tubule formation from single-cell suspensions; and 3) endothelial cell proliferation in immortalized endothelial cells and vessel explants. We hypothesized that Epo would induce mitogenesis and stimulate vasculogenesis in primary cultures of microvascular endothelial cells (MVECs) from neonatal rat mesentery. Isolation, purification, characterization, and culture of MVECs were performed. Cell proliferative effects of rhEpo were studied by 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in cultured MVECs. Vasculogenic effects of rhEpo were examined on cultured MVECs plated on either hormone-rich Matrigel substratum or the extracellular matrix protein, type I collagen. Our findings show that MVECs are isolated and purified, and that rhEpo stimulates MVEC proliferation, with maximal proliferation seen with a concentration of 50 IU/mL rhEpo. Tubule formation assays reveal that an rhEpo concentration of 50 IU/mL produces maximal tubule formation after 12 h on both Matrigel and the simple substratum, type I collagen. Our study is the first to examine the effects of rhEpo on the endothelium of the neonatal gastrointestinal tract. These data suggest that Epo may have a trophic effect on the vasculature of the gastrointestinal tract early in development. Furthermore, as Epo has been measured in breast milk, and its receptor has been shown to exist on the mucosa and gastrointestinal vasculature, Epo may be an endogenous stimulant of vessel growth during neonatal gastrointestinal development.     

Division of lymphatic vessels at varicocelectomy leads to testicular oedema and decline in testicular function according to the LH-RH analogue stimulation test

OBJECTIVES: To study the andrological outcome of the division of testicular lymphatic vessels at varicocelectomy in children and adolescents. METHODS: Testicular size and basal and stimulated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) values were determined prospectively in 86 patients with left unilateral varicocele grades II-III. 22 patients underwent lymphatic non-sparing surgery (LNS group), 10 of them with artery sparing (LNS/AS) and 12 without artery sparing (LNS/ANS), 23 patients underwent lymphatic sparing repair (LS group) and 41 patients were treated conservatively (NT group). RESULTS: The LNS group demonstrated significantly greater left testicular enlargement at six weeks and one year following repair, left testicular hypertrophy developed in 31.8% and hydrocele in 22.7% of patients. Marked oedema of intertubular tissue and a varying degree of tubular injury was observed in boys surgically treated for hydrocele. In the LS group, neither hypertrophy nor hydrocele developed postoperatively, the LH stimulated values were lower than in LNS/ANS group (p<0.05) and the NT group (p<0.04), the FSH stimulated values were lower than in the LNS/ANS group (p<0.001). CONCLUSIONS: Division of lymphatic vessels at varicocelectomy is associated with an excessive increase in testicular volume due to oedema, and with a reduced testicular function according to higher LH and FSH stimulated values. Preservation of lymphatics is strongly advised in varicocelectomy in adolescents to ensure better andrological outcome.     

Early detection of myocardial dysfunction in Chagas disease using novel echocardiographic indices

The first manifestation of cardiac involvement in Chagas disease could be sudden death or rapid deterioration in cardiac function. The aim of this study was to identify a non-invasive method for early detection of cardiac involvement in patients with Chagas disease. During a 6-month period in 2001, 133 people were studied using echocardiography and electrocardiography in Honduras; 88 were seropositive for Trypanosoma cruzi, of which 31 were asymptomatic, and 45 were seronegative controls. The echocardiographic assessment included geometrical and time interval derived indices. Patients with asymptomatic Chagas disease had increased left and right myocardial performance index (MPI) when compared with seronegative controls (P= 0.003 and P= 0.023, respectively) with 36% having a left MPI above the upper limit of the normal range. They also had a reduced diastolic posterior wall thickness (P= 0.005) and lower posterior wall thickness to left ventricular cavity (PWT:LVC) ratio (P= 0.002). Our results show that the MPI, a simple Doppler parameter, and the PWT:LVC ratio are useful in the early detection of myocardial involvement in asymptomatic patients with Chagas disease. These parameters could serve as useful screening tools and monitor the disease progression in these patients.     

The first potent and selective non-imidazole human histamine H4 receptor antagonists

Following the discovery of the human histamine H4 receptor, a high throughput screen of our corporate compound collection identified compound 6 as a potential lead. Investigation of the SAR resulted in the discovery of novel compounds 10e and 10l, which are the first potent and selective histamine H4 receptor antagonists to be described.