Time-dependent effects of ovarian steroids on tyrosine hydroxylase activity in the limbic forebrain of female rats

Summary In this work, we have studied the time-course of the effects of pharmacological administration of ovarian steroids on tyrosine hydroxylase (TH) activity in the limbic forebrain of ovariectomized rats. Administration of estradiol produced a late decrease in TH activity. This effect was found 24 hours after the last steroid injection, disappearing at 32 hours. It was antagonized by progesterone, since a single injection of this steroid to estradiol-pretreated rats reversed to control values the estradiol-induced decrease. Nevertheless, the administration of progesterone after estradiol treatment caused a short-time decrease in the limbic activity of TH, which was observed 4 hours after the last steroid injection, disappearing subsequently. On the other hand, the administration of progesterone alone produced a biphasic effect, with a reduction at 24 hours, followed by an increase at 32 hours. These effects were only observed in the animals non-treated with estradiol, disappearing with a previous treatment with estrogens. Hence, it can be concluded that both ovarian steroids may affect the limbic TH activity. Thus, estradiol produced a late inhibitory effect on the activity of this enzyme, which was antagonized by progesterone. Administration of the last one to estradiol-treated rats produced a short-time inhibitory effect, whereas its administration to non-treated rats produced a late biphasic effect (inhibition followed by stimulation), which was not observed in estradiol-treated rats.     

Gene expression patterns and profile changes pre- and post-erlotinib treatment in patients with metastatic breast cancer.

PURPOSE: To delineate gene expression patterns and profile changes in metastatic tumor biopsies at baseline and 1 month after treatment with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib in patients with metastatic breast cancer. EXPERIMENTAL DESIGN: Patients were treated with 150 mg of oral erlotinib daily. Gene expression profiles were measured with Affymetrix U133A GeneChip and immunohistochemistry was used to validate microarray findings. RESULTS: Estrogen receptor (ER) status by immunohistochemistry is nearly coincided with the two major expression clusters determined by expression of genes using unsupervised hierarchical clustering analysis. One of 10 patients had an EGFR-positive tumor detected by both microarray and immunohistochemistry. In this tumor, tissue inhibitor of metalloproteinases-3 and collagen type 1 alpha 2, which are the EGF-down-regulated growth repressors, were significantly increased by erlotinib. Gene changes in EGFR-negative tumors are those of G-protein-linked and cell surface receptor-linked signaling. Gene ontology comparison analysis pretreatment and posttreatment in EGFR-negative tumors revealed biological process categories that have more genes differentially expressed than expected by chance. Among 495 gene ontology categories, the significant differed gene ontology groups include G-protein-coupled receptor protein signaling (34 genes, P = 0.002) and cell surface receptor-linked signal transduction (74 genes, P = 0.007). CONCLUSIONS: ER status reflects the major difference in gene expression pattern in metastatic breast cancer. Erlotinib had effects on genes of EGFR signaling pathway in the EGFR-positive tumor and on gene ontology biological process categories or genes that have function in signal transduction in EGFR-negative tumors.     

Comparison of yogurt, soybean, casein, and amino acid–based diets in children with persistent diarrhea

Although previous studies have shown successful treatment of persistent diarrhea (PD) with the use of yogurt-based diets, some recent ones speculate the need of special formulas for the nutritional management of PD complicated cases. In the present study, we tested the hypothesis that the consumption of 3 lactose-free diets, with different degrees of complexity, is associated with lower stool output and shorter duration of diarrhea when compared with the use of a yogurt-based one on the nutritional management of PD. A total of 154 male infants, aged between 1 and 30 months, with PD and with or without dehydration, were randomly assigned to 1 of 4 treatment groups. Throughout the study, the patients were placed in a metabolic unit; their body weights and intakes of oral rehydration solution, water, and formula diets, in addition to outputs of stool, urine, and vomit, were measured and recorded at 24-hour intervals. Four different diets were used in this study: diet 1, yogurt-based formula; diet 2, soy-based formula; diet 3, hydrolyzed protein-based formula; and diet 4, amino acid–based formula. Throughout the study, only these formula diets were fed to the children. The data showed that children fed the yogurt-based diet (diet 1) or the amino acid–based diet (diet 4) had a significant reduction in stool output and in the duration of diarrhea. The use of an inexpensive and worldwide-available yogurt-based diet is recommended as the first choice for the nutritional management of mild to moderate PD. For the few complicated PD cases, when available, a more complex amino acid–based diet should be reserved for the nutritional management of these unresponsive and severe presentations. Soy-based or casein-based diets do not offer any specific advantage or benefits and do not seem to have a place in the management of PD.     

Age determines memory for face identity and expression

Background: The recognition of facial expressions is an important component of emotion processing which contributes to interactional behavior. One of the factors highly associated with potential decline of ability in behavioral tasks is age. Methods: We have investigated age‐related changes in facial identity and expression memory of healthy subjects in three age groups: young adults (20–40 years), elderly adults (60–80 years) and, for the first time in the literature, very old adults (over 80 years of age). Using a picture test, photographs of faces with happy or angry expressions were presented to study participants during the encoding task, and the memory for identity and emotional facial expression was investigated in a subsequent recognition task showing emotionally neutral faces. Half of the faces presented in the recognition task were initially shown in the encoding task. Results: Age interacted with the memory process: the ability to recognize both facial identity and emotional expression declined with advanced age. Happy facial expressions were better recognized in all age groups. Although there was a continuous overall decrease in recognition of both happy and angry expressions with advanced age, the effect favoring happy facial expressions was stable also in very old adults. Other factors such as gender or educational level did not affect the memory process for facial expressions. Conclusions: Our findings suggest that age is a significant determinant of memory for facial identity and emotional expression, and that, similar to younger adults, the recognition process of the elderly favors happy emotional facial expressions.     

Usher syndrome: clinical findings and gene localization studies

The issue of genetic heterogeneity is a critical problem in the localization of the gene(s) for Usher syndrome. Based on the data obtained on families studied to date, the differences between type I and type II Usher syndrome appear quite distinct with regard to auditory and vestibular function. Although the majority of families can be confidently diagnosed as typical type I or type II, clinical investigations revealed four families with findings that did not fit into either of the two more common subtypes. These findings emphasize the critical importance of an in-depth clinical analysis concomitant with the linkage investigation to assure accurate subtyping of Usher syndrome. Based on an analysis of only those families with definite type I or type II Usher syndrome, approximately 17% of the genome can be excluded as a potential site of the gene for type I, and 14% can be excluded as the site for the type II gene. This study will continue until the Usher gene(s) is successfully localized.     

Targeted routine asthma care in general practice using telephone triage

BACKGROUND: There is a high non-attendance rate for traditional clinic-based routine asthma care in general practice. Alternative methods of providing routine asthma care need to be examined. AIM: To examine the cost and effectiveness of targeted routine asthma care in general practice using telephone triage, compared to usual clinic care. DESIGN OF STUDY: An open randomised controlled trial. SETTING: A single semi-rural practice in the southwest of England. METHOD: Adult patients with asthma were randomised to receive either their routine asthma care in the surgery or care by telephone triage. Asthma control parameters, health status and NHS resource utilisation were measured over the 12-month study period. RESULTS: One hundred and ninety-four patients were randomised and 35% per cent more patients (n = 84 versus n = 62) received more than one consultation in the telephone group. Asthma control as measured by the asthma control questionnaire (ACQ) was similar in the clinic and telephone groups: mean change in ACQ = -0.11 (95% CI = -0.32 to 0.11) versus -0.18 (95% CI = -0.38 to 0.02). Mean NHS costs were 210 pounds sterling per patient per year in the telephone group compared to 334 pounds sterling in the clinic group (P-value of bootstrapped difference = 0.071). CONCLUSION: Targeted routine asthma care by telephone triage of adult asthmatics can lead to more asthma patients being reviewed, at less cost per patient and without loss of asthma control compared to usual routine care in the surgery.     

Isolation of Malassezia spp. from cerumen of wild felids.

The objective of this study was to determine the presence of different species of the genus Malassezia in the healthy external auditory canal of wild felids maintained in captivity. One hundred and thirty-two adult animals (264 samples of cerumen), 77 males (58.3%) and 55 females (41.7%), were studied: large felids (55 animals) - 26 lions (Panthera leo), 13 tigers (Panthera tigris), 6 leopards (Panthera pardus), 6 jaguars (Panthera onca), 2 cheetahs (Acinonyx jubatus), 2 pumas (Puma concolor); small felids (77 animals) - 29 tiger cats (Leopardus tigrinus), 19 jaguarundis (Herpailurus yagouaroundi), 10 margays (Leopardus wiedii), 9 pampas cats (Oncifelis colocolo), 6 geoffroy's cats (Oncifelis geoffroyi), and 4 servals (Leptailurus serval). Samples were obtained by the introduction of a sterile swab into the ear canal after cleaning the auricle with an alcohol-ether solution. The swabs were seeded onto Petri dishes containing modified Mycosel agar and sterile olive oil was added to the surface of the medium before specimen seeding. The plates were incubated at 35oC for two weeks. The isolates were analyzed regarding macro-and micromorphology and identified through catalase tests and growth on Tween 20, 40, 60 and 80. Malassezia spp. were isolated from 58 of the felids studied (43.9%) and from 102 samples of cerumen (38.6%). Malassezia sympodialis was isolated exclusively in large felids (33 animals-56.9%), and Malassezia pachydermatis exclusively in smaller varieties (25 animals - 43.1%). The incidence of fungi was higher in lions, with yeast being isolated in 25 of 26 animals (96.2%). Forty-eight strains (47.1%) were isolated from the right ear canal and 54 (52.9%) from the left. Although M. pachydermatis is the species considered a member of the microbiota of the mammalian external ear canal these results suggest that M. sympodialis participates in the microbiota of large felids.     

Opioid receptor binding in parahippocampus of patients with temporal lobe epilepsy: its association with the antiepileptic effects of subacute electrical stimulation.

Opioid receptor binding was evaluated in parahippocampal cortex (PHC) obtained from patients with intractable mesial temporal lobe epilepsy (MTLE) with and without subacute high frequency electrical stimulation (HFS) in this brain area. Mu, delta and nociceptin receptor binding was determined by autoradiography in PHC of five patients (ESAE group) with MTLE history of 14.8 +/- 2.5 years and seizure frequency of 11 +/- 2.9 per month, two of them (40%) with mesial sclerosis. This group demonstrated antiepileptic effects following subacute HFS (130 Hz, 450 micros, 200-400 microA), applied continuously during 16-20 days in PHC. Values were compared with those obtained from patients with severe MTLE (history of 21.7 +/- 2.8 years and seizure frequency of 28.2 +/- 14 per month) in whom electrical stimulation did not induce antiepileptic effects (ESWAE group, n = 4), patients with MTLE in whom no electrical stimulation was applied (MTLE group, n = 4) and autopsy material acquired from subjects without epilepsy (n = 4 obtained from three subjects). Enhanced 3H-DAMGO (MTLE, 755%; ESAE, 375%; ESWAE, 693%), 3H-DPDPE (MTLE, 242%; ESAE, 80%; ESWAE, 346%) and 3H-nociceptin (MTLE, 424%; ESAE, 217%; ESWAE, 451%) binding was detected in the PHC of all epileptic groups. However, tissue obtained from ESAE group demonstrated lower opioid receptor binding (3H-DAMGO, 44.5%, p < 0.05; 3H-DPDPE, 47%, p < 0.05; 3H-nociceptin, 39.3%, p < 0.5) when compared with MTLE group. The present results indicate that a high effectiveness to the antiepileptic effects induced by HFS is associated with reduced opioid peptide binding.