Effects of reversible inactivation of the dorsal hippocampus on the behavioral and cardiovascular responses to an aversive conditioned context

In rats, conditioned fear to context causes freezing immobility and cardiovascular changes. The dorsal hippocampus (DH) has a critical role in several memory processes, including conditioning fear to contextual information. To explore a possible involvement of the DH in contextual fear conditioning-evoked cardiovascular (mean arterial pressure and heart rate increases) and behavioral (freezing) responses, DH synaptic transmission was temporarily inhibited by bilateral microinjections of 500 nl of the nonselective synapse blocker, cobalt chloride (COCl2, 1 mmol/l), at different periods of the experimental procedure. During re-exposure to the foot shock chamber in which conditioning had taken place, bilateral DH inhibition 10 min before the conditioning session had no effect on either behavioral or cardiovascular responses. Bilateral DH inhibition immediately after the conditioning session (110 min) decreased both behavioral and cardiovascular responses during the context test. Finally, 48 h after the conditioning session, bilateral DH inhibition 10 min before re-exposure to the foot shock chamber significantly reduced cardiovascular responses but not freezing responses. These results suggest that contextual fear conditioning acquisition does not depend on the DH. This structure, however, is crucial for the consolidation of contextual fear. Moreover, although the DH appears to be less important for the behavioral (freezing) changes induced by re-exposure to the aversive conditioned context, it may play an important role on the cardiovascular responses generated by this model.

Organophosphate-related ototoxicity: Description of the vestibulocochlear system ultrastructural aspects of guinea pigs

Organophosphate toxic agents are used in agriculture and are currently part of the group of toxic agents which can lead to hearing loss, in which we have solvents, metals and asphyxiation agents. Aim: to analyze the acute ototoxic action of a group of organophosphate agents in the vestibulocochlear system. This is a prospective experimental study. Materials and Methods: we used male albino guinea pigs, broken down into three groups, to which we provided distilled water (group 1 - control), agrotoxic agent - 0.3mg/Kg/day (group 2), agrotoxic - 3 mg/Kg/day (group 3), during 7 seven consecutive days. The most used agrotoxic agent was Tamaron BR (metamidophos). The anatomical evaluation of the cochlea, saccule and utricle was carried out by means of electronic scanning microscopy after the use of the agrotoxic agent. Results: the guinea pigs submitted to the organophosphate presented cochlear morphological alterations with lesions on the three turns analyzed, as well as cilia alterations in the saccule and utricle, intensified according to the agent dosage. Conclusion: the morphological alterations seen in the hair cells exposed to daily doses of organophosphate promote evidences of an acute deleterious effect of agrotoxic agents on the vestibulocochlear system.

A functional study on gentamicin-related cochleotoxicity in its conventional dose in newborns

The early identification of hearing impairment allows for an intervention still in the ""critical"" and ideal period of hearing and language stimulation. Pediatric ototoxicity is a very controversial topic. There have been variable percentages of ototoxicity cases in children with different aminoglycosides antibiotics. The main pediatric groups whom receive aminoglycosides are newborns with severe infections on the neonatal ICU. Aim: to check the functional aspect of the cochlear external hair cells and treatment regimens used to treat infections during the neonatal period. Study design: Experimental. Materials and Methods: we studied 26 albino guinea pigs, through distortion product otoacoustic emissions, before and after the use of gentamicin. Results: in all the assessments, the external hair cells functional status, studied by means of the distortion product otoacoustic emissions, proved preserved. Conclusion: In the present study, we did not notice changes in outer hair cell function in the albino guinea pigs treated with gentamicin in the doses of 4 mg/Kg/ day and 2.5 mg/Kg/day every 12 hours for 10 and 14 days.

Gentamicin attenuates gentamicin-induced ototoxicity - Self-protection

Aminoglycoside antibiotics cause considerable toxicity to the inner ear. A progressive hearing loss at high frequencies resulted from the loss of hair cells in the base of the cochlea and a constant preoccupation with finding a treatment that protects against their toxic effects. A self-protection phenomenon to high ototoxic doses of gentamicin is proposed in this paper. Thirty-eight adult guinea pigs with normal hearing were tested using Preyer`s reflex and the distortion product otoacoustic emission (DPOAE) test, and their cochleae were analyzed by scanning electron microscopy. To the four groups investigated, group I (control) and group II (low dose, 10 mg/kg/day for 30 days) showed a normal DPOEA and normal outer hair cells; group III (high dose, 160 mg/kg/day for 10 days) showed the absence of DPOEA and damage to the outer hair cells; and group IV (low dose, 10 mg/kg/day for 30 days followed by a high dose of 160 mg/kg/day for 10 days) showed a normal DPOEA and normal outer hair cells. These results demonstrate that there was a considerable self-protection phenomenon by gentamicin.

Tactile threshold detection in leprosy patients with an electronic algometer

Objective: To propose an electronic method for sensitivity evaluation in leprosy and to compare it to the Semmes-Weinstein monofilaments. Methods:Thirty patients attending the Dermatology outpatient clinic of HCFMRP-USP were consecutively evaluated by both the electronic aesthesiometer and Semmes-Weinstein monofilaments on hand and foot test points. The intraclass correlation coefficient (ICC) was calculated to determine the variability of the electronic measures and the Kappa coefficient was calculated to determine the agreement between methods according to their categories (altered and non-altered tactile sensitivity). Results: The ICC was approximately 1, demonstrating repeatability. The Kappa coefficient showed more than 75 and 63% agreement on the hand and foot points, respectively. The mean agreement between the 2 methods for the 7 points of the right and left hand was 77.14 and 75.71%, respectively. The mean agreement for all 10 points was 74.33 and 63.66% on the right and left foot, respectively. In cases of disagreement the detection of altered tactile sensitivity by the electronic esthesiometer on the right and left foot was 90.91 and 84.25%, respectively, with no detection by the monofilaments. Conclusion: The results suggest that the electronic esthesiometer is a reliable and easy application, capable of evaluating alterations of tactile sensitivity in leprosy patients. (C) 2009 Elsevier B.V. All rights reserved.

Intestinal bacterial overgrowth after Roux-en-Y gastric bypass

The aim of the present study was to report the occurrence of serious subnutrition, associated to intestinal bacterial overgrowth, in two patients submitted to bariatric surgery. Two female patients (body mass index, 49 and 50 kg/m(2), respectively) were submitted to Y-en-Roux gastric bypass. The first patient evolved a 52% loss of body weight within 21 months after surgery; the other, a 34% loss of initial body weight within 15 months after surgery, results corresponding, respectively, to 62 and 45 kg weight losses. However, both patients reported asthenia, hair fallout, and edema, and one also reported diarrhea, but none was feverish. Their respective albuminemias were of 24 and 23 g/l. A respiratory hydrogen test suggested bacterial hyperproliferation. Thirty days after ciprofloxacin and tetracyclin treatments, they showed improved albumin levels and nutritional states, both confirmed by results of hydrogen breath tests. Bacterial overgrowth is an important complication that can compromise clinical evolution of patients submitted to intestinal surgery like gastroplasty with Y-Roux anastomosis. In cases of clinical suspicion or a confirmed diagnosis, adequate antibiotics, sometimes requiring to be cyclically repeated, should be administered.

Neuroendocrine, behavioral and macrophage activity changes induced by picrotoxin effects in mice

The relevance and property of studies related to stress effects on immune function are undisputable. All studies conducted on stress-immune relationships, however, provide from physical and/or psychological stressors. Indeed, as far as it is of our knowledge brain-innate immune responses were not analyzed after anxiogenic-like drugs use. The present experiment was then undertaken to analyze the effects of picrotoxin (0.3, 0.6 and 1.0 mg/kg doses) on behavior, macrophage activity, serum corticosterone and noradrenaline (NE) levels and turnover in the brain of adult mice. Results showed that picrotoxin treatment in mice: (1) decreased motor and rearing activities in an open-field; (2) decreased the number of entries into the plus-maze open-arms and decreased the time spent in the exploration of the plus-maze open-arms; (3) decreased both motor activity and the level of holes exploration in the hole-board; (4) increased the levels of serum corticosterone in dose-dependent way; (5) increased noradrenaline (NE) and MHPG levels and NE turnover in the hypothalamus; and (6) increased Staphylococcus aureus and PMA-induced macrophage oxidative burst. However, and contrary to that reported after physical or psychological stress, this drug induced no effects on macrophage phagocytosis and NE levels and turnover in the frontal cortex. The present results are thus showing that picrotoxin induces some but not all neuro-innate immunity changes previously reported for inescapable foot-shock and psychological stressors in mice. These facts suggest that this chemical stressor triggers CNS pathways that might be somehow different from those fired by inescapable foot-shock and psychological stressors, leading to different neuro-innate immune responses. (C) 2007 Elsevier Ltd. All fights reserved.

Postpartum ovarian activity of Santa Ines lactating ewes fed diets containing soybean hulls as a replacement for coastcross (Cynodon sp.) hay

The Santa Ines, a Brazilian hair sheep, has a non-seasonal breeding activity. Data regarding the duration of the postpartum anestrous period in Santa Ines lactating ewes is lacking and the objective of this trial was to determine the effects of replacing neutral detergent fibre (NDF) provided by coastcross (Cynodon sp.) hay with NDF contained in soybean hulls (SH) on the postpartum ovarian activity-as measured by the serum progesterone (P(4)) concentration. Fifty-six lactating ewes (body weight 56.1 +/- 6.8 kg) were individually penned and used in a randomized complete block design with 14 blocks and four treatments. The SH NDF replaced 33 (SH33), 67 (SH67), or 100% (SH100) of the NDF contributed by coastcross hay in the control diet (SHO). This resulted in a SH inclusion at rates of 0, 25, 54, and 85% of the dietary dry matter (DM). Blood samples were collected twice weekly from the 14th to 84th day postpartum and the serum P(4) concentrations determined by radioimmunoassay (RIA). It was estimated that the 1st postpartum ovulation occurred 6 days before the date that a serum P(4) >= 1 ng/ml concentration was first recorded. The mean body condition score (BCS; 0-5 scale) was 3.0 +/- 0.19 on day 14 postpartum and the mean BCS at day 56 postpartum increased linearly (P<0.01) with the inclusion levels of SH (3.09, 3.24, 3.34, and 3.36, respectively). Treatments did not differ significantly in the induction of postpartum days to the resumption of ovarian luteal activity (34.1 +/- 15.3 days postpartum). On days 25, 50, and 75 postpartum 36.80, and 100% of the ewes had resumed ovarian activity, respectively. Nonesterified fatty acid concentration decreased quadratically (P<0.05) with the SH inclusion, with values of 0.323, 0.244, 0.204, and 0.216 mequiv./l for the SHO, SH33, SH67, and SH100 treatments being recorded, respectively. Replacement of the NDF provided by coastcross hay with the NDF from the SH did not influence the duration of the postpartum anestrous period in Santa Ines lactating ewes. Considering a 150-day gestation period and the 34 days postpartum anestrous demonstrated in the present study, the current production system of a lambing interval of 8 months (3 lambing events in 2 years) may not be optimizing the production potential and a system in which the lambing interval is shortened by at least 1 month may be feasible. (C) 2008 Elsevier B.V. All rights reserved.

Differences in thermoregulatory ability between slick-haired and wild-type lactating Holstein cows in response to acute heat stress

Animals inheriting the slick hair gene have a short, sleek, and sometimes glossy coat. The objective of the present study was to determine whether slick-haired Holstein cows regulate body temperature more effectively than wild-type Holstein cows when exposed to an acute increase in heat stress. Lactating slick cows (n = 10) and wild-type cows (n = 10) were placed for 10 h in an indoor environment with a solid roof, fans, and evaporative cooling or in an outdoor environment with shade cloth and no fans or evaporative cooling. Cows were exposed to both environments in a single reversal design. Vaginal temperature, respiration rate, surface temperature, and sweating rate were measured at 1200, 1500, 1800, and 2100 h (replicate 1) or 1200 and 1500 h (replicate 2), and blood samples were collected for plasma cortisol concentration. Cows in the outdoor environment had higher vaginal and surface temperatures, respiration rates, and sweating rates than cows in the indoor environment. In both environments, slick-haired cows had lower vaginal temperatures (indoor: 39.0 vs. 39.4 degrees C; outdoor 39.6 vs. 40.2 degrees C; SEM = 0.07) and respiration rate (indoor: 67 vs. 79 breaths/min; outdoor 97 vs. 107 breaths/min; SEM = 5.5) than wild-type cows and greater sweating rates in unclipped areas of skin (indoor: 57 vs. 43 g.h(-1)/m(2); outdoor 82 vs. 61 g.h(-1)/m(2); SEM = 8). Clipping the hair at the site of sweating measurement eliminated the difference between slick-haired and wild-type cows. Results indicate that slick-haired Holstein cows can regulate body temperature more effectively than wild-type cows during heat stress. One reason slick-haired animals are better able to regulate body temperature is increased sweating rate.

MC1R genotype modifies risk of melanoma in families segregating CDKN2A mutations

Mutations in the exons of the cyclin-dependent kinase inhibitor gene CDKN2A are melanoma-predisposition alleles which have high penetrance, although they have low population frequencies. In contrast, variants of the melanocortin-1 receptor gene, MC1R, confer much lower melanoma risk but are common in European populations. Fifteen Australian CDKN2A mutation-carrying melanoma pedigrees were assessed for MC1R genotype, to test for possible modifier effects on melanoma risk. A CDKN2A mutation in the presence of a homozygous consensus MC1R genotype had a raw penetrance of 50%, with a mean age at onset of 58.1 years. When an MC1R variant allele was also present, the raw penetrance of the CDKN2A mutation increased to 84%, with a mean age at onset of 37.8 years (P=0.1). The presence of a CDKN2A mutation gave a hazard ratio of 13.35, and the hazard ratio of 3.72 for MC1R variant alleles was also significant. The impact of MC1R variants on risk of melanoma was mediated largely through the action of three common alleles, Arg151Cys, Arg160Trp, and Asp294His, that have previously been associated with red hair, fair skin, and skin sensitivity to ultraviolet light.

Melanocortin-1 receptor genotype is a risk factor for basal and squamous cell carcinoma

MC1R gene variants have previously been associated with red hair and fair skin color, moreover skin ultraviolet sensitivity and a strong association with melanoma has been demonstrated for three variant alleles that are active in influencing pigmentation: Arg151Cys, Arg160Trp, and Asp294His. This study has confirmed these pigmentary associations with MC1R genotype in a collection of 220 individuals drawn from the Nambour community in Queensland, Australia, 111 of whom were at high risk and 109 at low risk of basal cell squamous cell carcinoma. Comparative allele frequencies for nine MC1R variants that have been reported in the Caucasian population were determined for these two groups, and an association between prevalence of basal cell carcinoma, squamous cell carcinoma, solar keratosis and the same three active MC1R variant alleles was demonstrated [odds ratio=3.15 95% CI (1.7, 5.82)]. Three other commonly occurring variant alleles: Val60Leu, Val92Met, and Arg163Gln were identified as having a minimal impact on pigmentation phenotype as well as basal cell carcinoma and squamous cell carcinoma risk. A significant heterozygote effect was demonstrated where individuals carrying a single MC1R variant allele were more likely to have fair and sun sensitive skin as well as carriage of a solar lesion when compared with those individuals with a consensus MC1R genotype. After adjusting for the effects of pigmentation on the association between MC1R variant alleles and basal cell carcinoma and squamous cell carcinoma risk, the association persisted, confirming that presence of at least one variant allele remains informative in terms of predicting risk for developing a solar-induced skin lesion beyond that information gained through observation of pigmentation phenotype.

The expression of fibroblast growth factors and their receptors in the embryonic and neonatal mouse inner ear

Four different fibroblast growth factor receptors (FGFR) are known, three of which have splice variants (known as the b and c variants) in the FGF-binding domain, to give different patterns of sensitivity to the different FGFs. The expression of the b and c variants of the FGF receptors. together with the expression of the ligands FGF1. FGF2, FGF3, FGF7, FGF8b and FGF8c, was determined by quantitative reverse transcription-polymerase chain reaction in developing whole mouse inner ears, and in dissected components of the postnatal mouse inner ear. At embryonic age (E)10.5 days, when the otocyst is a simple closed sac, the receptor most heavily expressed was FGFR2b, relative to the postnatal day 0 level. Over the period E10.5-E12.5. during which the structures of the inner ear start to form, the expression of the different FGF receptors increased 10(2)-10(4) fold per unit of tissue, and there was a gradual switch towards expression of the 'c' splice variants of FGFR2 and FGFR3 rather than the 'b' variants. At E10.5, the ligands most heavily expressed, relative to the postnatal day 0 level, were FGF3, FGF8b and FGF8c. In the postnatal inner eat. the patterns of expression of receptors and ligands tended to be correlated, such that receptor variants were expressed in the same regions as the ligands that are known to activate them effectively. The neural/sensory region expressed high levels of FGFR3c, and high levels of the ligand FGF8b. The same area also expressed high levels of FGFR1b and FGFR2b, and high levels of FGF3. The lateral wall of the cochlea (including the stria vascularis and the spiral ligament) expressed high levels of FGFR1c and FGF1. 11 is suggested that the different FGF receptors and ligands are expressed in a spatially coordinated pattern to selectively program cochlear development. (C) 2001 Elsevier Science B.V. All rights reserved.