Gender identity in patients with 5-alpha reductase deficiency raised as females.

BACKGROUND AND OBJECTIVE: 5-Alpha reductase type 2 deficiency (5-ARD) is a rare disorder of sex development. The lack of 5-alpha reductase, an enzyme that converts testosterone into dihydrotestosterone, results in external genitalia that may appear female, or predominantly male, albeit undervirilized, or, more often, ambiguous. METHODS: This study describes a series of patients with 5-ARD raised as female, focusing on aspects related to gender identity. Following a retrospective chart review, patients with 5-ARD were invited to return to the clinic to enable their gender identity to be assessed using an 11-item structured in-house questionnaire. The Golombok-Rust Inventory of Sexual Satisfaction was applied to patients who had initiated their sexual life. RESULTS: Six patients aged >15 years with 5-ARD and raised as female were included. Most patients were diagnosed late: two before and four after puberty. The mean length of the phallus was 2.8 cm (0.5-5.0). Reasons for seeing a doctor included genital appearance (n = 3), amenorrhea/absence of breast development (n = 2), and changes in gender role attitudes (n = 1). According to the gender identity assessment, 4 patients identified as female, 1 as male, and 1 as both genders. Only the patient identified as male requested gender re-assignment. Of the two patients who had initiated their sexual life, sexual satisfaction was found to be good in one and poor in the other due to vaginal discomfort during intercourse. CONCLUSION: In the present series, the majority of undervirilized patients with a diagnosis of 5-ARD raised as female were in complete conformation with being female and described themselves as heterosexual. The more virilized patients were those least in conformity with their female-assigned gender.

Macro- and microstructural descriptions of the zebrafish (Danio rerio) liver.

The liver is an essential metabolically active organ, responsible for many vital life functions such as metabolism, synthesis, and storage. This study describes the macroscopic and microscopic zebrafish liver and its temporal changes during a period of 13 weeks. Forty-six adult zebrafish were used (46), of which 27 were females and were 19 males. Seven fish were euthanized initially for macroscopic evaluation and 3 fish were euthanized weekly for 13 weeks for microscopic evaluation. Routine histological technique was performed; the slides were stained with haematoxylin/eosin and periodic acid-Schiff. The volumetric (Vv(h)) and numerical (Nv(h)) densities of hepatocytes and vacuolation intensity were determined weekly. The liver was located in the coelomic cavity ventrally to the swim bladder, slightly brownish and divided into 3 hepatic lobes. Microscopically, it consisted of hepatocytes forming a muralium duplex around the sinusoids. The staining of the cytoplasm of hepatocytes was more eosinophilic and more basophilic in males and females, respectively. There was no formation of portal triads and phagocytic cells. The gallbladder had transitional epithelium, and the bile ducts had simple cuboidal epithelium. The volume and numerical density of hepatocytes during the 13 weeks was not statistically different, but these parameters displayed a positive correlation. The vacuolation was due to the presence of glycogen. The zebrafish liver has macro and micro structural particular features while, quantitatively, the volume and number of hepatocytes showed great capacity to respond to the physiological needs of the animal at the time.

Gabaergic and opioid receptors mediate the facilitation of NaCl intake induced by α2-adrenergic activation in the lateral parabrachial nucleus.

Alpha2-adrenergic, gabaergic or opioidergic activation in the lateral parabrachial nucleus (LPBN) increases sodium intake. In the present study, we investigated the effects of single or combined blockade of opioidergic and gabaergic receptors in the LPBN on the increase of 0.3M NaCl intake induced by α2-adrenoceptor activation in the LPBN. Male Holtzman rats (n=5-9/group) with cannulas implanted bilaterally in the LPBN were treated with the diuretic furosemide (10 mg/kg b wt.) combined with low dose of the angiotensin converting enzyme inhibitor captopril (5 mg/kg b wt.) subcutaneously. Bilateral injections of moxonidine (alpha2-adrenergic/imidazoline receptor agonist, 0.5 nmol) into the LPBN increased furosemide+captopril-induced 0.3M NaCl intake (25.8±1.4, vs. vehicle: 3.8±1.1 ml/60 min). The opioidergic receptor antagonist naloxone (100 nmol) or the GABAA receptor antagonist bicuculline (5 nmol) injected into the LPBN partially reduced the increase of 0.3M NaCl intake produced by LPBN moxonidine (11.8±4.0 and 22.8±4.5, respectively, vs. vehicle+moxonidine: 31.6±4.0 ml/60 min, respectively). Similar to the treatment with each antagonist alone, the combined injections of naloxone (100 nmol) and bicuculline (5 nmol) into the LPBN also partially reduced moxonidine effects on 0.3M NaCl intake (15.5±6.5 ml/60 min). The GABAB receptor antagonist saclofen (5 nmol) injected into the LPBN did not change the effects of moxonidine on 0.3M NaCl intake (24.3±7.8 ml/120 min). These results suggest that the increase of 0.3M NaCl intake by α2-adrenergic receptor activation in the LPBN is partially dependent on GABAA and opioid receptor activation in this area.

Chemoreflex control of the cardiovascular system remains altered after recovery from low protein diet early in life.

This study aimed to evaluate the cardiovascular component of the arterial chemoreflex in rats recovered from low protein diet. Male Fischer rats were randomly divided into control and recovered (R-PR) groups after weaning. R-PR rats were fed with low protein diet for 35days and recovered under normal protein diet for 70days. Control rats received normal protein diet for 105days. Arterial chemoreflex was elicited by intravenous injection of KCN. Results showed that pressor response of the chemoreflex was increased in R-PR. Data suggest that protein restriction may alter cardiovascular response to chemical activation of the chemoreflex after recovery.

Baclofen into the lateral parabrachial nucleus induces hypertonic sodium chloride and sucrose intake in rats.

GABA(A) and GABA(B) receptors are present in the lateral parabrachial nucleus (LPBN), a pontine area involved with inhibitory mechanisms related to the control of sodium appetite. Activation of GABA(A) receptors in the LPBN induces strong ingestion of 0.3 M sodium chloride (NaCl) in normonatremic and euhydrated rats. In the present study, we investigated the effects of the GABA(B) receptor agonist baclofen, injected alone or combined with GABA(A) or GABA(B) receptor antagonists into the LPBN on 0.3 M NaCl, water, 0.06 M sucrose and food intake in normonatremic and euhydrated rats. Male Holtzman rats with stainless steel cannulas implanted bilaterally in the LPBN were used. In normonatremic and euhydrated rats, bilateral injections of baclofen (0.5 nmol/0.2 µl) into the LPBN induced 0.3 M NaCl (24.0±3.1 vs. saline: 2.0±0.8 ml/240 min) and water intake (10.6±1.4 vs. saline: 3.5±0.7 ml/240 min) in a two-bottle test. Injections of GABA(B) receptor antagonists CGP 35348 (50 nmol/0.2 µl) or 2-hydroxysaclofen (5 nmol/0.2 µl) or GABA(A) receptor antagonist bicuculline (1.6 nmol/0.2 µl) into the LPBN reduced 0.3 M NaCl (14.1±4.7 ml/240 min; 9.97±2.5 ml/210 min; 8.8±5.9 ml/240 min, respectively) and water intake induced by baclofen injected into the LPBN. Baclofen (0.5 nmol/0.2 µl) injected into the LPBN also induced 0.06 M sucrose intake (21.8±5.9 vs. saline: 5.0±2.6 ml/180 min). Urinary volume and sodium excretion had a tendency to decrease after baclofen injection into the LPBN, whereas arterial pressure and food intake were not affected. The results show that baclofen injected into the LPBN, in normonatremic and euhydrated rats, produces a natriorexigenic effect dependent on GABA(A) and GABA(B) receptor activation. The natriorexigenic effect is not secondary to alterations in blood pressure or sodium urinary excretion. In addition, baclofen injected into the LPBN also induces 0.06 M sucrose intake.

Opioid activation in the lateral parabrachial nucleus induces hypertonic sodium intake.

Opioid mechanisms are involved in the control of water and NaCl intake and opioid receptors are present in the lateral parabrachial nucleus (LPBN), a site of important inhibitory mechanisms related to the control of sodium appetite. Therefore, in the present study we investigated the effects of opioid receptor activation in the LPBN on 0.3 M NaCl and water intake in rats. Male Holtzman rats with stainless steel cannulas implanted bilaterally in the LPBN were used. In normohydrated and satiated rats, bilateral injections of the opioid receptor agonist beta-endorphin (2 nmol/0.2 microl) into the LPBN induced 0.3 M NaCl (17.8+/-5.9 vs. saline: 0.9+/-0.5 ml/240 min) and water intake (11.4+/-3.0 vs. saline: 1.0+/-0.4 ml/240 min) in a two-bottle test. Bilateral injections of the opioid antagonist naloxone (100 nmol/0.2 microl) into the LPBN abolished sodium and water intake induced by beta-endorphin into the LPBN and also reduced 0.3 M NaCl intake (12.8+/-1.5 vs. vehicle: 22.4+/-3.1 ml/180 min) induced by 24 h of sodium depletion (produced by the treatment with the diuretic furosemide s.c.+sodium deficient food for 24 h). Bilateral injections of beta-endorphin into the LPBN in satiated rats produced no effect on water or 2% sucrose intake when water alone or simultaneously with 2% sucrose was offered to the animals. The results show that opioid receptor activation in the LPBN induces hypertonic sodium intake in satiated and normohydrated rats, an effect not due to general ingestive behavior facilitation. In addition, sodium depletion induced 0.3 M NaCl intake also partially depends on opioid receptor activation in the LPBN. The results suggest that deactivation of inhibitory mechanisms by opioid receptor activation in the LPBN releases sodium intake if excitatory signals were activated (sodium depletion) or not.

Noradrenaline and mixed alpha 2-adrenoceptor/imidazoline-receptor ligands: effects on sodium intake.

The effect of noradrenaline, and mixed ligands to alpha 2-adrenoceptors (alpha 2-AR) and imidazoline receptors (IR), injected intracerebroventricularly (i.c.v.), on sodium intake of sodium depleted rats, was tested against idazoxan, a mixed antagonist ligand to alpha 2-AR and IR. The inhibition of sodium intake induced by noradrenaline (80 nmol) was completely reversed by idazoxan (160 and 320 nmol) injected i.c.v. The inhibition of sodium intake induced by mixed ligands to alpha 2-AR and IR, UK14,304, guanabenz and moxonidine, was antagonized from 50 to 60% by idazoxan i.c.v. The results demonstrate that noradrenaline, a non-ligand for IR, acts on alpha 2-AR inhibiting sodium intake. The possibility that either alpha 2-AR or IR mediate the effect of mixed agonists on sodium intake remains an open question.

Trauma in pregnant women: analysis of maternal and fetal mortality.

Twenty-seven traumatised pregnant women were analysed retrospectively over a period of 9 years. Mean age was 23.7 years (16-42 years). Gestational age ranged from 10 to 40 weeks (mean, 21.5 weeks), with most victims (46.1%) being in the second trimester. The predominant mechanism (65.3%) was blunt abdominal injury due to an automobile accident (the patient being run over or collision). At admission, 8 (30.7%) patients had haemodynamic alterations. 6 patients (23.0%) presented vaginal bleeding and 4 of these were haemodynamically normal. We analysed maternal mortality, fetal mortality and their causes. We also compared the median RTS and TRISS values for the groups with maternal-fetal survival and the group with maternal-fetal death. Fetal death occurred in all pregnant women admitted with vaginal bleeding. Maternal mortality due to haemorrhagic shock was 11.5%. Fetal mortality was 30.7%, with 37.5% of these deaths being caused by maternal death. The major cause of fetal mortality was a detached placenta (50.0%). The trauma indices, RTS and TRISS, were significantly lower (p = 0.0025 and p < 0.0001) in the group of maternal-fetal death but they were not of prognostic value in terms of fetal mortality.

Salivary Streptococcus mutans and caries prevalence in Brazilian schoolchildren.

The aim of the present study was to determine the levels of salivary Streptococcus mutans in Brazilian schoolchildren, and its possible correlation with caries prevalence. A positive correlation between different levels of S. mutans and caries prevalence was observed, individuals with high levels of S. mutans (greater than 100 colonies) had a DMFS significantly higher than those with low or no detectable S. mutans (0, 1-20, 21-40 colonies).