Dopamine depletion in wistar rats with epilepsy.

The dopamine content in cerebral structures has been related to neuronal excitability and several approaches have been used to study this phenomenon during seizure vulnerability period. In the present work, we describe the effects of dopamine depletion after the administration of 6-hidroxidopamine (6-OHDA) into the substantia nigra pars compacta of male rats submitted to the pilocarpine model of epilepsy. Susceptibility to pilocarpine-induced status epilepticus (SE), as well as spontaneous and recurrent seizures (SRSs) frequency during the chronic period of the model were determined. Since the hippocampus is one of main structures in the development of this experimental model of epilepsy, the dopamine levels in this region were also determined after drug administration. In the first experiment, 62% (15/24) of 6-OHDA pre-treated rats and 45% (11/24) of those receiving ascorbic acid as control solution progressed to motor limbic seizures evolving to SE, after the administration of pilocarpine. Severeness of seizures during the model´s the acute period, was significantly higher in epileptic experimental rats (56.52%), than in controls (4.16%). In the second experiment, the frequency of seizures in the model's chronic phase did not significantly change between groups. Our data show that dopamine may play an important role on seizure severity in the pilo's model acute period, which seems to be due to dopamine inhibitory action on motor expression of seizure.

Interaction of central angiotensin II and aldosterone on sodium intake and blood pressure.

Recent studies demonstrated an important natriorexigenic mechanism activated by aldosterone acting in the hindbrain. Studies have also shown that aldosterone effects are intensified by angiotensin II (ANG II) and vice-versa. Thus, the aim of the present work was to test if angiotensinergic mechanisms in the forebrain are involved on sodium appetite to aldosterone infused into the 4th V and also if aldosterone into the 4th V might facilitate ingestive and cardiovascular responses to central ANG II. Male Holtzman rats with stainless steel cannulas implanted into the 4th ventricle (4th V) and lateral ventricle (LV) had access to 1.8% NaCl during 2 h/day. Chronic infusion of aldosterone (100 ng/h) into the 4th V for 7 days strongly increased 1.8% NaCl intake (16.1 ±â€¯2.2 ml/2h/day). Losartan (AT1 receptor antagonist, 50 µg/1 µl) acutely injected into the LV reduced 1.8% NaCl intake induced by aldosterone infusion into the 4th V (8.8 ±â€¯2.3 ml/2h/day). The pressor response to ANG II (50 ng/1 µl) into the LV increased in rats treated with aldosterone into the 4th V (45 ±â€¯5 mmHg, vs. vehicle infusion: 26 ±â€¯4 mmHg). Similarly, fluid intake (water + 1.8% NaCl) also increased when rats receiving aldosterone infusion were treated with ANG II acutely into the LV. These results suggest that forebrain angiotensinergic mechanisms are important for sodium intake produced by aldosterone acting in the hindbrain. In addition, aldosterone in the hindbrain produces sensitization of the central pressor mechanisms activated by ANG II acting in the forebrain.

Aldosterone infusion into the 4th ventricle produces sodium appetite with baroreflex attenuation independent of renal or blood pressure changes.

Aldosterone infusion into the 4th ventricle (4th V), upstream the nucleus of the solitary tract (NTS), produces strong 0.3 M NaCl intake. In the present study, we investigated whether aldosterone infusion into the 4th V activates HSD2 neurons, changes renal excretion, or alters blood pressure and cardiovascular reflexes. Chronic infusion of aldosterone (100 ng/h) into the 4th V increased daily 0.3 M NaCl intake (up to 44 ±â€¯10, vs. vehicle: 5.6 ±â€¯3.4 ml/24 h) and also c-Fos expression in HSD2 neurons in the NTS and in non-HSD2 neurons in the NTS. Natriuresis, diuresis and positive sodium balance were present in rats that ingested 0.3 M NaCl, however, renal excretion was not modified by 4th V aldosterone in rats that had no access to NaCl. 4th V aldosterone also reduced baroreflex sensitivity (-2.8 ±â€¯0.5, vs. vehicle: -5.1 ±â€¯0.9 bpm/mmHg) in animals that had sodium available, without changing blood pressure. The results suggest that sodium intake induced by aldosterone infused into the 4th V is associated with activation of NTS neurons, among them the HSD2 neurons. Aldosterone infused into the 4th V in association with sodium intake also impairs baroreflex sensitivity, without changing arterial pressure.

Rapid stimulation of sodium intake combining aldosterone into the 4th ventricle and the blockade of the lateral parabrachial nucleus.

Chronic infusion of aldosterone into the 4th ventricle (4th V) induces robust daily sodium intake, whereas acute injection of aldosterone into the 4th V produces no sodium intake. The inhibitory mechanism of the lateral parabrachial nucleus (LPBN) restrains sodium intake induced by different natriorexigenic stimuli and might affect the acute response to aldosterone into the 4th V. In the present study, 1.8% NaCl and water intake was tested in rats treated with acute injections of aldosterone into the 4th V combined with the blockade of the inhibitory mechanisms with injections of moxonidine (α2 adrenergic/imidazoline agonist) or methysergide (a serotonergic antagonist) into the LPBN. Male Holtzman rats with stainless steel cannulas implanted in the 4th V and bilaterally in the LPBN were used. Aldosterone (250 or 500ng) into the 4th V combined with vehicle into the LPBN induced no 1.8% NaClintake compared to control (1.5±1.1 and 1.1±0.4, respectively, vs. vehicle into 4th V: 1.0±0.5ml/2h). However, aldosterone (250 or 500ng) into the 4th V combined with moxonidine (0.5nmol) into the LPBN induced strong ingestion of 1.8% NaCl (12.7±4.6 and 17.6±3.7ml/2h, respectively). Aldosterone (250ng) into the 4th V combined with methysergide (4µg) into the LPBN also induced 1.8% NaCl intake (17.6±5.4ml/2h). These data suggest that the inhibitory mechanisms of the LPBN counteract the facilitation of sodium intake produced by aldosterone injected into the 4th, restraining sodium intake in this condition.

A review of the genus Dysalotus (Percomorphacea: Chiasmodontidae), with the description of Dysalotus pouliulii sp. nov.

A new species of Dysalotus (family Chiasmodontidae) known only from off the Hawaiian archipelago is described here as Dysalotus pouliulii sp. nov. It differs from all other species of Dysalotus in having a greater number of teeth on the premaxilla (151-198 v. 60-138) and dentary (136-199 v. 76-132) and in a shorter upper jaw [51·9-54·9% of head length (LH ) v. 62·4-74·4% LH ] and lower jaw (64·8-67·4% in LH v. 75·3-88·1% in LH ). A key for the species of Dysalotus and an updated distribution map are provided. http://zoobank.org/urn:lsid:zoobank.org:pub:E9B5F1DC-52E0-4F53-9109-2A8E252AE8CE.

Hydrogen peroxide attenuates the dipsogenic, renal and pressor responses induced by cholinergic activation of the medial septal area.

Cholinergic activation of the medial septal area (MSA) with carbachol produces thirst, natriuresis, antidiuresis and pressor response. In the brain, hydrogen peroxide (H2O2) modulates autonomic and behavioral responses. In the present study, we investigated the effects of the combination of carbachol and H2O2 injected into the MSA on water intake, renal excretion, cardiovascular responses and the activity of vasopressinergic and oxytocinergic neurons in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Furthermore, the possible modulation of carbachol responses by H2O2 acting through K+ATP channels was also investigated. Male Holtzman rats (280-320 g) with stainless steel cannulas implanted in the MSA were used. The pre-treatment with H2O2 in the MSA reduced carbachol-induced thirst (7.9±1.0, vs. carbachol: 13.2±2.0 ml/60 min), antidiuresis (9.6±0.5, vs. carbachol: 7.0±0.8 ml/120 min,), natriuresis (385±36, vs. carbachol: 528±46 µEq/120 min) and pressor response (33±5, vs. carbachol: 47±3 mmHg). Combining H2O2 and carbachol into the MSA also reduced the number of vasopressinergic neurons expressing c-Fos in the PVN (46.4±11.2, vs. carbachol: 98.5±5.9 c-Fos/AVP cells) and oxytocinergic neurons expressing c-Fos in the PVN (38.5±16.1, vs. carbachol: 75.1±8.5 c-Fos/OT cells) and in the SON (57.8±10.2, vs. carbachol: 102.7±7.4 c-Fos/OT cells). Glibenclamide (K+ATP channel blocker) into the MSA partially reversed H2O2 inhibitory responses. These results suggest that H2O2 acting through K+ATP channels in the MSA attenuates responses induced by cholinergic activation in the same area.

Persistent glucocorticoid resistance in systemic lupus erythematosus patients during clinical remission.

Glucocorticoids (GCs) are key drugs in the treatment of systemic lupus erythematosus (SLE). GC dose reduction during remission is related to disease activity, GC dose used, length of treatment, and individual GC sensitivity. We compared GC receptor α (GRα) isoform and nuclear factor kappaB (NF-κB) messenger RNA quantitation and in vivo GC sensitivity between SLE patients during remission and healthy controls. We performed a cross-sectional study of 19 women aged 22-49 years, including 9 SLE patients in clinical remission taking ≤5 mg prednisone and 10 matched controls. We evaluated GC sensitivity using 2 cortisol suppression tests: a very-low-dose intravenous dexamethasone suppression test (VLD-IV-DST) and a low-dose oral dexamethasone suppression test. GRα and NF-κB mRNA were quantified using real-time polymerase chain reaction. Although basal cortisol and adrenocorticotropic hormone levels were similar between the groups, the percentage of cortisol reduction after the VLD-IV-DST was 56% lower in SLE patients than in controls (P = 0.014). GRα and NF-κB gene expression levels were similar between the groups. The low-dose oral dexamethasone test caused intense cortisol suppression in all individuals, limiting the ability of this test to discriminate individual GC sensitivity. A positive correlation was found between the extent of cortisol suppression in vivo (VLD-IV-DST) and the number of days elapsed since the last flare of lupus activity. Despite clinical remission, SLE patients displayed partial GC resistance recognized by the VLD-IV-DST. The mechanism of this resistance is unrelated to altered GRα and NF-κB mRNA expression.

Increased androgen receptor messenger RNA in frontal-parietal hair follicles of women with androgenetic alopecia.

Normal testosterone levels are frequently observed in women with androgenetic alopecia (AGA), suggesting the involvement of androgen sensitivity in this condition. Androgen sensitivity is related to androgen receptor (AR) messenger RNA (mRNA) production in hair follicles and is negatively related to the number of CAG repeats present in exon 1 of the AR gene. The aim of this study was to compare AR expression in AGA women with normal controls and to correlate this expression with the number of CAG repeats. Hair follicles were obtained from 27 women with AGA and 21 controls for AR gene expression analysis. AR expression was evaluated through AR mRNA quantification using real-time polymerase chain reaction and the number of CAG repeats in the AR gene was determined in complementary DNA samples obtained from hair follicles and analyzed with the Gene Scan software. AR mRNA in the frontal-parietal region was significantly higher than in the occipital region of AGA patients (paired t-test, P = 0.046). No significant difference was identified in controls (P = 0.67). Both regions in the same individual showed a significant positive correlation in AGA patients (r = 0.77; P < 0.05) and in controls (r = 0.91; P < 0.05). A negative correlation was identified between AR expression and the number of CAG repeats only in AGA patients (r = 0.510; P = 0.013). The identification of elevated AR mRNA quantitation in hair follicles is a useful tool for identifying potentially abnormal androgen sensitivity in AGA patients.

Tissue-specific adaptive levels of glucocorticoid receptor alpha mRNA and their relationship with insulin resistance.

Insulin resistance is an underlying cause of metabolic changes associated with cardiovascular diseases. Glucocorticoids are known determinant factors of insulin resistance. We quantified glucocorticoid receptor alpha (GRα) mRNA and 11 beta-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) mRNA in various tissues of 35 patients with previously established cardiovascular disease. This was a prospective study in a cardiac surgery patient setting. Samples of subcutaneous adipose tissue, epicardial fat, muscle, and peripheral blood mononuclear cells were examined. GRα and 11ß-HSD1 mRNA were determined by real-time PCR. Mean age was 54.4 years. A significantly higher level of GRα mRNA was observed in muscle, with mean = 43.6 arbitrary units, median (p25-p75) = 39.4, compared to epicardial adipose tissue, with mean = 34.2, median (p25-p75) = 27.6, and to subcutaneous adipose tissue, with mean = 29.0, median (p25-p75) = 19.0, and lymphocytes, with mean = 17.5, median (p25-p75) = 14.02. When patients with diabetes mellitus were compared to patients without insulin resistance, significantly lower levels of GRα mRNA were observed in epicardial fat. Lymphocytes had the lowest 11ß-HSD1 mRNA concentration. We also observed significantly reduced 11ß-HSD1 mRNA levels in visceral fat when compared with muscle tissue. GRα and 11ß-HSD1 mRNA levels differed among tissues involved in the pathophysiology of metabolic syndrome. We conclude that epicardial adipose tissue has lower GRαmRNA levels in insulin-resistant patients; this seems to be an adaptive and protective mechanism.

Comparative in vitro and in vivo antimalarial activity of the indole alkaloids ellipticine, olivacine, cryptolepine and a synthetic cryptolepine analog.

Indole alkaloids ellipticine (1), cryptolepine triflate (2a), rationally designed 11-(4-piperidinamino)cryptolepine hydrogen dichloride (2b) and olivacine (3) (an isomer of 1) were evaluated in vitro against Plasmodium falciparum and in vivo in Plasmodium berghei-infected mice. 1-3 inhibited P. falciparum (IC50≤1.4 µM, order of activity: 2b>1>2a>3). In vitro toxicity to murine macrophages was evaluated and revealed selectivity indices (SI) of 10-12 for 2a and SI>2.8×10² for 1, 2b and 3. 1 administered orally at 50mg/kg/day was highly active against P. berghei (in vivo inhibition compared to untreated control (IVI)=100%, mean survival time (MST)>40 days, comparable activity to chloroquine control). 1 administered orally and subcutaneously was active at 10 mg/kg/day (IVI=70-77%; MST=27-29 days). 3 exhibited high oral activity at ≥50 mg/kg/day (IVI=90-97%, MST=23-27 days). Cryptolepine (2a) administered orally and subcutaneously exhibited moderate activity at 50mg/kg/day (IVI=43-63%, MST=24-25 days). At 50 mg/kg/day, 2b administered subcutaneously was lethal to infected mice (MST=3 days) and moderately active when administered orally (IVI=45-55%, MST=25 days). 1 and 3 are promising compounds for development of antimalarials.

Evaluation of the agreement by examiners according to classifications of third molars.

OBJECTIVES: This study recorded and evaluated the intra- and inter-group agreement degree by different examiners for the classification of lower third molars according to both the Winter's and Pell & Gregory's systems. STUDY DESIGN: An observational and cross-sectional study was realized with forty lower third molars analyzed from twenty digital panoramic radiographs. Four examiner groups (undergraduates, maxillofacial surgeons, oral radiologists and clinical dentists) from Aracaju, Sergipe, Brazil, classified them in relation to angulation, class and position. The variance test (ANOVA) was applied in the examiner findings with significance level of p<0.05 and confidence intervals of 95%. RESULTS: Intra- and inter-group agreement was observed in Winter's classification system among all examiners. Pell & Gregory's classification system showed an average intra-group agreement and a statistical significant difference to position variable in inter-group analysis with greater disagreement to the clinical dentists group (p<0.05). CONCLUSIONS: High reproducibility was associated to Winter's classification, whereas the system proposed by Pell & Gregory did not demonstrate appropriate levels of reliability.

Quantitation of glucocorticoid receptor alpha and NF-κB pathway mRNA and its correlation with disease activity in rheumatoid arthritis patients.

We measured NF-κB, IKK, c-Fos, and GRα mRNA expression and in vivo glucocorticoid sensitivity in patients with rheumatoid arthritis. A very low dose intravenous dexamethasone suppression test and real-time PCR quantitation of mRNA of these genes were performed on blood samples from 21 rheumatoid arthritis patients who were not on glucocorticoids during the previous four months and on blood samples from 20 healthy individuals. Mean rheumatoid arthritis duration was 8.8 years, and mean disease activity, as assessed by Disease Activity Score 28 (DAS28), was 4.45. Basal cortisol and the percentage of cortisol reduction after the very low dose intravenous dexamethasone suppression test, as well as NF-κB, IKK, c-Fos, and GRα mRNA expression, were similar among groups. We did not observe significant correlations between glucocorticoid in vivo sensitivity and DAS28. There was a positive correlation between DAS28 and NF-κB, IKK, and GRα, but not c-Fos. In the multivariate analysis, only NF-κB mRNA remained as an independent variable for predicting DAS28.

Applicability of real-time PCR methodology in the neonatal detection of Turner syndrome.

Turner syndrome (TS) is the complete or partial loss of the second sex chromosome, occurring in 1:5 000 girls. Early recognition allows appropriate therapy for short stature and puberty. Neonatal diagnosis of TS permits detection of associated malformations, minimizing sequels. Aiming to develop a molecular method for the diagnosis of TS we employed blood samples stored on filter paper. We evaluated 78 female controls, 25 TS girls with 45,X karyotype, and 32 TS patients with other karyotypes. After DNA extraction, samples were submitted to real-time PCR, using primers and probes directed to the study gene ARSE and to the control gene GAPDH. A ROC curve established the ARSE:GAPDH ratio with a cutoff value of 0.7. Low ARSE:GAPDH ratio of <0.7 was present in 100% of 45,X TS patients. This cutoff value presented a sensitivity of 100% and a specificity of 100% in detecting 45,X TS patients with a positive predictive value of 100% and a negative predictive value of 100%. The same cutoff value was able to identify only 56% of TS with other karyotypes, in which we observed a mean (SD) ARSE:GAPDH ratio=0.66 (0.2); and the interquartile range=0.4-0.8. Determination of ARSE:GAPDH ratio is a fast, sensitive, and specific method, with viable cost and feasible automation, which makes it potentially applicable in neonatal screening programs for the diagnosis of Turner syndrome 45,X.

The effect of carbon and nitrogen sources on bovicin HC5 production by Streptococcus bovis HC5.

AIMS: To investigate the effect of media composition and agroindustrial residues on bovicin HC5 production by Streptococcus bovis HC5. METHODS AND RESULTS: Batch cultures of S. bovis HC5 were grown in basal medium containing different carbon and nitrogen sources. The activity of cell-free and cell-associated bovicin HC5 was determined in culture supernatants and acidic extracts obtained from cell pellets, respectively. Streptococcus bovis HC5 produced bovicin using a variety of carbon and nitrogen sources. The highest specific activity was obtained in media containing 16 g l(-1) of glucose, after 16 h of incubation. The peak in cell-free and cell-associated bovicin HC5 activity was detected when S. bovis HC5 cultures reached stationary phase. The bovicin HC5 specific activity and bacterial cell mass increased approximately 3-fold when yeast extract and trypticase (0.5 and 1.0 g l(-1), respectively) were added together to the basal medium. Streptococcus bovis HC5 cultures produced bovicin HC5 in cheese whey and sugar cane juice and maximal volumetric productivity was obtained after 12 h of incubation. CONCLUSIONS: Streptococcus bovis HC5 is a versatile lactic acid bacterium that can utilize several carbon and nitrogen sources for bovicin HC5 production. This bacterium could be a useful model to study bacteriocin production in the rumen ecosystem. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of agroindustrial residues as carbon sources could have an economical impact on bovicin HC5 production. To our knowledge, this is the first report to show the use of sugar cane juice for bacteriocin production by lactic acid bacteria.

Impact of prolonged physical training on the pituitary glucocorticoid sensitivity determined by very low dose intravenous dexamethasone suppression test.

The activity of the hypothalamic-pituitary-adrenal axis is usually modulated by several stress factors, including exercise. Different responses are induced by physical training according to duration and intensity of exercise. During prolonged training, cortisol remains normal or decreased as a consequence of altered cortisol secretion, metabolism and excretion, and possibly by changes in glucocorticoid sensitivity. The aim of this study was to evaluate the impact of prolonged physical training on the glucocorticoid sensitivity. Eighteen cadets of the Air Force Academy, mean (SD) age: 18.7 (1.0) years, underwent an intensive 6-week preparatory training-period considered adequate by inducing significant changes on body composition measured by bioelectrical impedance. Measurement of individual's pituitary glucocorticoid sensitivity was done by an intravenous very low dose dexamethasone suppression test (20 microg/m (2)) that was performed before and after the training period. Cortisol levels were obtained at basal condition and 120 minutes after the dexamethasone infusion. Basal cortisol showed a significant decrease after prolonged training. The percent cortisol suppression after dexamethasone tended to be lower after the training period. Overall, our data suggest that prolonged physical training is able to reduce glucocorticoid sensitivity, which can have a beneficial impact in chronic stress conditions.

Structural evaluation of type 3 dopaminergic receptor gene (DRD3) in chronic anovulatory women.

Dopamine receptor type 3 (DRD3) expressed in the limbic system sites involved in the regulation of GnRH seems to play a role in neuroendocrine control. We hypothesized that women with chronic anovulation should show exacerbated secretion of prolactin (PRL) after thyrotropin-releasing hormone (TRH) stimulation test, having more chances for dopamine inhibitory dysfunction due to alterations in the structure of DRD3. The DRD3-coding region was evaluated in 60 women with chronic anovulation (35 without and 25 with hyperresponse of PRL after TRH stimulation), and in 34 controls. Statistically similar frequencies of homozygous AGC polymorphism (43.4 and 33.4%) and heterozygous polymorphism (33.4 and 47.9%) at position 9 were found in controls and patients, respectively. Homozygous GCG polymorphism at position 17 was identified in 3.4% of the patients, while heterozygosis occurred in 20.8% of the patients and in 6.6% of the controls. The novel 41563_41567delTAAGT polymorphism of DRD3 was identified in 14.7% of the controls and 8.6% of the women with chronic anovulation displaying hyperresponse of PRL after TRH stimulation. Alteration 41563_41567delTAAGT of DRD3 was not found in patients who did not show hyperresponse of PRL after TRH stimulation. Normal baseline and peak levels of PRL and thyroid-stimulating hormone were similar for women with and without 41563_41567delTAAGT in the DRD3 gene. It is concluded that the novel polymorphism in DRD3 identified in this study is not associated with the response of PRL to TRH stimulation in women with chronic anovulation.

Structural evaluation of type 3 dopaminergic receptor gene (DRD3) in chronic anovulatory women

Dopamine receptor type 3 (DRD3) expressed in the limbic system sites involved in the regulation of GnRH seems to play a role in neuroendocrine control. We hypothesized that women with chronic anovulation should show exacerbated secretion of prolactin (PRL) after thyrotropin-releasing hormone (TRH) stimulation test, having more chances for dopamine inhibitory dysfunction due to alterations in the structure of DRD3. The DRD3-coding region was evaluated in 60 women with chronic anovulation (35 without and 25 with hyperresponse of PRL after TRH stimulation), and in 34 controls. Statistically similar frequencies of homozygous AGC polymorphism (43.4 and 33.4%) and heterozygous polymorphism (33.4 and 47.9%) at position 9 were found in controls and patients, respectively. Homozygous GCG polymorphism at position 17 was identified in 3.4% Type 3 dopaminergic receptor in chronic anovulationof the patients, while heterozygosis occurred in 20.8% of the patients and in 6.6% of the controls. The novel 41563_41567delTAAGT polymorphismof DRD3 was identified in 14.7% of the controls and 8.6% of the women with chronic anovulation displaying hyperresponse of PRL after TRH stimulation. Alteration 41563_41567delTAAGT of DRD3 was not found in patients who did not show hyperresponse of PRL after TRH stimulation. Normal baseline and peak levels of PRL and thyroid-stimulating hormone were similar for women with and without 41563_41567delTAAGT in the DRD3 gene. It is concluded that the novel polymorphism in DRD3 identified in this study is not associated with the response of PRL to TRH stimulation in women with chronic anovulation.

A novel mutation in DAX1 gene causing different phenotypes in three siblings with adrenal hypoplasia congenita.

Adrenal hypoplasia congenita (AHC) is a rare disease that can be caused by many abnormalities, including an X-linked form. Mutations in the DAX1 gene have been assigned as the genetic cause of AHC. We describe here three siblings with AHC, clinically presented at different ages, two in the neonatal period and one oligosymptomatic during infancy. Molecular analysis was able to detect a novel mutation in exon 1 of the DAX1 gene, consisting of a transition of C to T at position 359, determining a stop codon at position 359 (Q359X). The mutated gene encodes a truncated protein missing a large portion of the ligand-binding domain (C-terminal domain). The recognition of the disease in the index case suggested the diagnosis in the other siblings. Interestingly, the same mutation is presented with different phenotypes, suggesting that first-degree family members of patients with DAX1 mutations should be carefully evaluated routinely.

A novel mutation in DAX1 gene causing different phenotypes in three siblings with adrenal hypoplasia congenita

Adrenal hypoplasia congenita (AHC) is a rare disease that can be caused by many abnormalities, including an X-linked form. Mutations in the DAX1 gene have been assigned as the genetic cause of AHC. We describe here three siblings with AHC, clinically presented at different ages, two in the neonatal period and one oligosymptomatic during infancy. Molecular analysis was able to detect a novel mutation in exon 1 of the DAX1 gene, consisting of a transition of C to T at position 359, determining a stop codon at position 359 (Q359X). The mutated gene encodes a truncated protein missing a large portion of the ligand-binding domain (C-terminal domain). The recognition of the disease in the index case suggested the diagnosis in the other siblings. Interestingly, the same mutation is presented with different phenotypes, suggesting that first-degree family members of patients with DAX1 mutations should be carefully evaluated routinely.

On the dielectric behaviour of collagen-algal sulfated polysaccharide blends: effect of glutaraldehyde crosslinking.

In this paper, impedance measurements in the frequency range from 10(-2) to 10(6) Hz are presented for collagen and algal sulfated polysaccharide crosslinked films. We are considering the development of new biomaterials which have potential applications in coating of cardiovascular prostheses, support for cellular growth and in systems for controlled drug delivery. The effect of crosslink sulfated polysaccharide on the physical chemical properties of collagen was studied using FT-infrared spectroscopy, differential scanning calorimetry (DSC), dielectric spectroscopy. The resulting films crosslinked with glutaraldehyde (GA) in concentrations of 0.001% and 0.05% when analysed by DSC, showed that the GA treatment not only left the thermal stability of the collagen unaffected, but it also decreased the thermal transition energy. Dielectric spectroscopy shows that the effect of the crosslink on the blend film was associated to the decrease and stabilization of the dielectric permittivity at low frequencies and decreased its conductivity.