Bupropion induced changes in exploratory and anxiety-like behaviour in NMRI male mice depends on the age.

The aim of this study was to assess the effects of the antidepressant bupropion on anxiety and novelty-seeking in adolescent mice of different ages and adults. Behavioural differences between early adolescent, late adolescent and adult NMRI mice were measured both in the elevated plus-maze and the hole-board tasks following acute administration of bupropion (5, 10, 15, 20mg/kg) or saline. In the plus maze test, early and late adolescent mice treated with bupropion (10, 15mg/kg, respectively) had lower percentages of entries in the open-arms compared to their vehicle controls. Adult mice treated with bupropion did not differ from their vehicle controls. These results suggest that the effect of this drug on anxiety-like behaviour in mice depends on the age, showing adolescents an anxiogenic-like profile. In the hole-board, adolescents showed more elevated levels of novelty-seeking than adults, exhibiting shorter latency to the first head-dip (HD) and a higher number of HD's. Bupropion increases the latency to the first HD and decreases the number of HD's in all age-groups, indicating a decline in exploratory tendency. Findings reveal that the age can modulate the behaviour displayed by mice in both animal models, and that adolescents are more sensitive to bupropion's anxiogenic effects.

Resistencia a hormonas tiroideas no asociada a mutación de la isoforma beta del receptor de hormonas tiroideas: caso clínico / Thyroid hormone resistance not associated to mutation on the beta isoform of the thyroid hormone receptor: report of one case

Thyroid hormone resistance (RTH) is inherited as an autosomal dominant trait, with variable clinical presentations. The hallmark of the syndrome is a variable degree of resistance to thyroid hormones, with high levels of circulating thyroid hormones, inappropriately normal or elevated TSH values and a clinical pattern of mixed hypothyroidism and hyperthyroidism. RTH is related in more than 85 percent of cases to thyroid hormone beta receptor mutations. We report a 11 years female with a history of treatment with propylthiouracil (PTU) for hyperthyroidism, presenting with a progressive goiter. Thyroidectomy was performed, removing 233 grams of thyroid tissue showing follicular hyperplasia. After surgery, a fast growth of the remnant thyroid gland was observed along with tachycardia. Laboratory showed a TSH of 38 mU/mL a triiodothyronine level of 300 ng/dL a thyroxin level of 14.8 ug/dL and a free thyroxin of 3.19 ng/dL, suggesting the diagnosis of RTH. The molecular study was negative for mutation of the beta isoform of thyroid hormone receptor. The possible theories that can explain these findings are discussed.

Simultaneous cell death and upregulation of poly(ADP-ribose) polymerase-1 expression in early postnatal mouse retina.

PURPOSE: Poly(ADP-ribose) polymerase (PARP)-1 is a nuclear enzyme that transfers ADP-ribose units (PAR polymer) to nuclear proteins and has been implicated in caspase-independent cell death in different models of retinal degeneration. The involvement of PARP-1 in cell death occurring during normal postnatal development of the mouse retina was investigated. In addition, the expression of apoptosis-inducing factor (AIF), a caspase-independent cell death mediator, was explored because PARP-1 activation has been related to the translocation of a 57-kDa form of AIF into the cell nucleus. METHODS: Cell death was determined in retinas of developing mice by both ELISA and TUNEL. PARP-1, PAR, and AIF were analyzed by immunocytochemistry and immunoblotting. Quantification of PARP-1 mRNA levels was also performed by real-time PCR. RESULTS: PARP-1 upregulation and PAR polymer formation, indicative of PARP-1 activity, were observed during the first postnatal week simultaneously with the presence of abundant dying cells, some of which were not associated with active caspase-3. PARP-1 was downregulated and PARP-1 activity progressively declined in the retina during subsequent postnatal development, coinciding with the decrease in cell death. Truncated AIF (57 kDa) was present in the retina during the first postnatal week, gradually decreasing thereafter, and had a nuclear localization in some cells, which also showed strong PAR polymer nuclear staining. CONCLUSIONS: These results show that a caspase-independent cell death pathway exists during the normal development of the mouse retina and suggest that PARP-1 participates in this cell death pathway by mediating AIF translocation to the cell nucleus.

Radioterapia como indicación post operatoria en macroadenomas hipofisiarios no funcionantes: a propósito de un caso / Surgical treatment of a non functioning pituitary macroadenoma without postoperative radiotherapy: report of one case

We report a 45 years old female that consulted for amenorrhea and galactorrhea after discontinuing oral contraceptives, that she used for several years. The patient had hyperprolactinemia, a hypogonadotrophic hypogonadism and a primary hypothyroidism. Sella turcica magnetic resonance showed a pituitary macroadenoma with a diameter of 23 mm and supraselar extension. The patient was subjected to a transsphenoidal excision of the tumor with good clinical and surgical results. Therefore radiotherapy was not used for the treatment of the tumor.

Individual differences in novelty-seeking and behavioral responses to nicotine: a review of animal studies.

Individual differences in the behavioral responses to a novel environment have been proposed as a research tool to predict responsiveness to other behavioral tasks, response to certain events and individual vulnerability to nicotine addiction. In rats and mice, novelty seeking (defined as enhanced specific exploration of novel situations) is a complex behavior confirmed by a large body of neurochemical, endocrinological and behavioral data. We review the main standardized procedures employed to measure the novelty seeking trait in rodents and the ontogeny of this behavior throughout the life-span taking into account that novelty seeking can be permanently modified as a consequence of particular early experiences, maternal care, and environmental enrichment. Studies in animal models suggest that individual differences in the sensitivity to nicotine depend on different variables such as basal locomotor activity of the experimental subjects, their response to novel environments (open-field, hole-board) and level of impulsivity. It is concluded that these basic findings contribute to a better understanding of smoking behavior and to the establishment of improved pharmacological treatments if individual differences are borne in mind.

Resultados Terapéuticos en pacientes acromegálicos: es tiempo de intervenir / Results of surgical treatment for acromegaly in 53 patients

Background: The treatment of choice for acromegaly is surgery that, according to the literature, is curative in 91 percent of pituitary microadenomas and 73 percent of macroadenomas. Aim: To report the results of surgical treatment in 53 patients with acromegaly. Material and methods: Retrospective review of medical records of all patients with acromegaly, operated between 1984 and 2004. When necessary, patients were contacted by telephone to complete information or to perform biochemical or imaging studies. A normal value of insulin like growth factor I (IGF-1) for age and sex, a growth hormone (GH) nadir of less than 1 ng/ml during a glucose tolerance test or a basal GH of less than 2.5 ng/ml, all assessed three months after surgery, were considered as criteria for cure. Results: Biochemical cure was achieved in 67 percent of patients with pituitary microadenomas and 21 percent of patients with macroadenomas. In 47 percent of patients with neuro-ophtalmological involvement, a partial or total recovery in the visual field defect was achieved. The most common surgical complications were transient diabetes insipidus in 19 percent, persistent diabetes insipidus in 4 percent and cerebrospinal fluid fistula in 4 percent. A lower size of the tumor and lower preoperative growth hormone levels were associated with a better chance of cure. Conclusions: The cure rates obtained in this group of patients are clearly lower than those reported abroad. These results stress the importance of having a national registry of acromegaly and the need to train neurosurgeons in the treatment of pituitary tumors.

Effects of co-administration of bupropion and nicotinic agonists on the elevated plus-maze test in mice.

There is evidence that the cholinergic nicotinic system is involved in the modulation of anxiety. Anxiolytic and anxiogenic effects of nicotine agonists have been reported in mice. Bupropion is an antidepressant drug which may alleviate some symptoms of nicotine withdrawal, although its effects on anxiety are not clear. It has been suggested that the interaction between bupropion and nicotinic mechanisms could be complex. The aim of the present study was to investigate acute effects of co-administration of bupropion and nicotinic agonists on the elevated plus-maze test in NMRI mice. Effects of nicotine, lobeline, and cytisine (0.35 and 0.175 mg/kg), administered alone or combined with bupropion (20 mg/kg) were tested in the plus-maze. Results indicated that nicotine (0.35 mg/kg) decreased number and percentage of entries and time spent in open arms, and increased percentage of protected stretched attend posture. Bupropion (20 mg/kg) plus lobeline (0.175 mg/kg) increased percentage of time spent in open arms, without altering total or closed arm entries. Our findings suggest that the highest dose of nicotine induces anxiogenic effects, which are counteracted when co-administered with bupropion. The combination of bupropion with a low dose of lobeline seems to have an anxiolytic profile in the conventional parameters of the plus-maze, although ethological measures do not support it clearly.

Bupropion effects on aggressiveness and anxiety in OF1 male mice.

RATIONALE: Bupropion is an antidepressant drug that is being used to help in giving up smoking. Its behavioral effects have been evaluated in different animal models, although limited information is available regarding its effects on aggressiveness, anxiety and exploratory behavior. OBJECTIVES: Evaluate acute effects of bupropion on locomotor activity, isolation-induced aggression, hole-board and elevated plus-maze tests in OF1 male mice. METHODS: In the first experiment, effects of bupropion (2.5, 5, 10, 20 and 40 mg/kg) on locomotion were evaluated. In the second experiment, isolation-induced aggression was assessed in isolated male mice previously classified as short attack latency (SL) and long attack latency (LL). Mice were treated with bupropion or vehicle and confronted with standard opponents for 10 min. In experiments 3 and 4, mice were treated with bupropion or vehicle and 30 min later examined in the plus-maze or in the hole-board apparatus. RESULTS: In the actimeter, bupropion induced a dose-dependent increase in locomotion. During agonistic encounters, bupropion (10 mg/kg and 40 mg/kg) increased time devoted to attack in LL mice. In the plus-maze, no significant differences were found between bupropion-treated and vehicle-treated mice in the percentage of entries or time spent in open arms. In the hole-board, the highest dose of bupropion (40 mg/kg) significantly decreased number of head-dips and increased latency to the first head-dip. CONCLUSIONS: During agonistic encounters the two sub-groups of mice (SL and LL) may display differential sensitivity in drug-induced changes on aggressiveness, since bupropion increased attack only in mice with "long attack latency" in the pre-screening test. In the plus-maze, this drug does not seem to have specific actions on anxiety and in the hole-board a high dose had similar effects to those induced by anxiogenic drugs.

Effects of acute administration of bupropion on behavior in the elevated plus-maze test by NMRI mice.

Bupropion attenuates some symptoms of nicotine abstinence, although its effects on anxiety are unclear. The present study investigates acute effects of bupropion (5, 10, 20 and 40 mg/kg) on anxiety as expressed in the elevated plus-maze test in male NMRI mice. Given the influence of locomotion in this test, effects of bupropion were also evaluated in an actimeter. Spontaneous motor activity remained significantly increased in mice treated with 10, 20 and 40 mg/kg of bupropion during the 60 min recorded. Results from the elevated plus-maze showed that 20 mg/kg increased total arm entries and 40 mg/kg increased total and open arm entries. Although the increase in the number of visits to the open arms suggests an anxiolytic-like effect, if the actions of this drug on locomotion are taking into account, one may conclude that the increase in open arm entries observed with the highest doses is a motor effect rather than anxiolysis per se. In addition, ethological measures failed to detect a clear anxiolytic profile since neither a significant decrease in total stretched attend postures nor a reduction in the percentage of protected forms of head dipping or stretched attend postures were observed at any dose tested. These results suggest that the elevated plus-maze is sensitive to the motor actions of bupropion and that this should be taken into account in the evaluation of the "emotional" effects of this drug.

¿Pseudohipoparatiroidismo o déficit de vitamina D? / Pseudohypoparathyroidism or vitamin D deficiency? Report of one case

Pseudohypoparathyroidism is characterized by a resistance to parathormone, with variable phenotypical and biochemical manifestations. Its diagnosis is difficult. We report a 28 years old male presenting with a hypokalemic periodic paralysis. His serum PTH was elevated to 1,343 and 1,101 pg/ml with concomitant hypocalcemia of 7.9 and 6.7 mg/dl. Twenty four hour urinary calcium and serum 25 hydroxy vitamin D were normal. Bone mineral density was normal. The patient was managed with calcitriol in doses of 1 to 2 µg/d, associated to calcium 2 g/day. Serum calcium levels and PTH normalized after two months and six months of treatment respectively.

Effects of early training and nicotine treatment on the performance of male NMRI mice in the water maze.

This research aimed to evaluate the effect of nicotine treatment and prior training on a spatial learning task in differently aged NMRI male mice. In a longitudinal study, mice were randomly assigned to one of 14 experimental groups receiving different combinations of chronically injected nicotine (0.35 mg/kg) administered for 10 days (5 days before and during 5 days acquisition of task) or control treatments and training in the water maze at different ages. The mice displayed shorter escape latencies when evaluated at 6 and 10 months than when tested in this task at 2 months for the first time, demonstrating that early training preserves performance in the water maze up to 8 months after the initial experience. Nicotine treatment did not significantly change performance in the water maze at any age tested. Early practice in a spatial reference memory task appears to have lasting consequences and can potentially contribute to preventing some age-related spatial learning deficits.

A specific anti-aggressive effect of repeatedly administered lobeline.

The effects of chronic treatments with nicotinic agonists on agonistic encounters have received little attention. The effects of repeated (for 10 days) SC administration of (-)-lobeline (9.3, 18.6 and 37.2 micromol/kg) and (-)-nicotine (0.93, 1.86 and 3.72 micromol/kg) were evaluated using the mouse isolation-induced aggression model. Individually housed OF1 male mice served as experimental animals and were confronted by 'standard opponents'. Each mouse was tested only once on the last day of the repeated drug treatment. Videotaped agonistic encounters were analysed estimating the times allocated to 11 behavioural categories. Repeated treatment with the highest dose of lobeline diminished attack behaviour without significantly increasing immobility or changing any other behavioural category involving motor activity. In contrast, nicotine did not significantly alter time allocated to any behavioural category.

Hipertiroidismo gestacional: análisis a propósito de un asociado a mola / Gestational hyperthyroidism associated to molar pregnancy: a case report

We report a 18 years old woman that was admitted with a history of four days of cardiac failure with acute pulmonary edema, high blood pressure, left ventricular dilatation and moderate to severe systolic dysfunction. Twenty four hours after admission she had a miscarriage, expelling a mole. The diagnosis of hyperthyroidism caused by a mole and early pre eclampsia was confirmed and the patient was managed with diuretics and dopamine. Symptoms abated, thyroid function tests, cardiac function and size returned to normal values and the patient was discharged asymptomatic, ten days after admission