Immunoneutralization of gonadotropin-releasing hormone type-III suppresses male reproductive behavior of cichlids

To investigate the roles of gonadotropin-releasing hormone (GnRH) types in reproductive behaviors, antisera against GnRH1, GnRH2 and GnRH3 were stereotaxically administered into the intracerebroventricular region to neutralize the three native GnRH types in the brain of male tilapia Oreochromis niloticus. Reproductive behaviors (nest-building and aggressive behaviors), and morphological changes of the three GnRH systems were investigated by immunocytochemistry. GnRH1, GnRH2 and GnRH3 immunoreactive fibers were significantly decreased following injections of GnRH antisera indicating successful neutralization of their respective endogenous GnRH peptides. GnRH1- and GnRH2-immunoneutralization did not inhibit reproductive behaviors but GnRH3-immunoneutralization significantly decreased nest-building ability (Saline: 26.5 ± 3.7%/day versus GnRH3: 6.1 ± 2.9%/day, P < 0.001), nest size (Saline: 0.67 ± 0.09 points versus GnRH3: 0.10 ± 0.05 points, P < 0.0002) and aggressive behavior (Saline: 2.34 ± 0.19 points versus GnRH3 1.06 ± 0.12 points, P < 0.0001). These observations provide evidence that GnRH3 is a potent neuromodulator of reproductive behaviors in male tilapia.     

Development of a behaviour change communication tool for medical students: The ‘Tent Pegs’ booklet

Objective

To describe the development and validation of a behaviour change communication tool for medical students.

Methods

Behaviour change techniques (BCTs) were identified within the literature and used to inform a communication tool to support medical students in discussing health-related behaviour change with patients. BCTs were organized into an accessible format for medical students (the ‘Tent Pegs’ booklet) and validated using discriminant content validity methods with 11 expert judges.

Results

One-sample t-tests showed that judges reliably mapped BCTs onto six of the seven Tent Pegs domains (confidence rating means ranged from 4.0 to 5.1 out of 10, all p ≤ 0.002). Only BCTs within the ‘empowering people to change’ domain were not significantly different from the value zero (mean confidence rating = 1.2, p > 0.05); these BCTs were most frequently allocated to the ‘addressing thoughts and emotions’ domain instead.

Conclusion

BCTs within the Tent Pegs booklet are reliably allocated to corresponding behaviour change domains with the exception of those within the ‘empowering people to change’ domain.

Practice implications

The existing evidence-base on BCTs can be used to directly inform development of a communication tool to support medical students facilitate health behaviour change with patients.     

Patient-provider communication and reproductive health among HIV-positive women in Rio de Janeiro, Brazil

Objective

To qualitatively assess the influence of patient-provider communication on contraceptive choice among HIV-positive women in the context of universal antiretroviral therapy (ART) access.

Methods

Focus group discussions (FGD; n = 3), in-depth (IDI; n = 15) and freelist interviews (FLI; n = 36) were conducted with HIV-positive women aged 18-40 years recruited from public health units in Rio de Janeiro/Brazil.

Results

Of 70 participants, 49 used ART and the median time since HIV diagnosis was 6 years (range: 1-18). The majority of participants (71.4%) reported some degree of dissatisfaction with their health providers (usually lack of open dialogue) and a few reported experiences of stigma/prejudice during appointments. Intra, interpersonal and social factors modulated behaviors and reproductive health decisions, and those issues were rarely addressed by providers during HIV clinical care.

Conclusion

Despite dramatic increases in survival and life quality after universal ART implementation in Brazil, reproductive health issues are neglected by multiple cadres of HIV health providers. Communication on reproductive health issues remains fragmented and potentially contradictory, compromising care in these settings.

Practice implications

Adequate provider training to address reproductive health-related issues in a comprehensive, culturally sensitive manner and improved integration of HIV and reproductive health care are urgently needed in this setting.     

Impact of two types of Internet-based information on medical students’ performance in an Objective Structured Clinical Exam (OSCE)

Objectives

Internet-based information has potential to impact physician–patient relationships. This study examined medical students’ interpretation and response to such information presented during an objective clinical examination.

Method

Ninety-three medical students who had received training for a patient centered response to inquiries about alternative treatments completed a comprehensive examination in their third year. In 1 of 12 objective structured clinical exams, a SP presented Internet-based information on l-theanine – an amino acid available as a supplement. In Condition A, materials were from commercial websites; in Condition B, materials were from the PubMed website.

Results

Analyses revealed no significant differences between Conditions in student performance or patient (SP) satisfaction. Students in Condition A rated the information less compelling than students in Condition B (z = −1.78, p = .037), and attributed less of the treatment's action to real vs. placebo effects (z = −1.61, p = .053).

Conclusions

Students trained in a patient centered response to inquiries about alternative treatment perceived the credibility of the two types of Internet-based information differently but were able to respond to the patient without jeopardizing patient satisfaction. Approach to information was superficial. Training in information evaluation may be warranted.     

Central ghrelin treatment stimulates ACTH cells in normal-fed,food-restricted and high-fed rats: An immunohistomorphometric and hormonal study

Changes in feeding regime represent serious stress, while ghrelin is considered a key player in energy balance. We investigated the effects of intracerebroventricular (ICV) ghrelin application on pituitary adrenocorticotropic (ACTH) cells in rats fed diets differing in energy content. Before the ICV treatment, male Wistar rats were subjected to three different feeding regimes for 4 weeks: normal-fed (NF), food-restricted (FR) or high-fed (HF) (n = 3 × 14). At the age of 8 weeks, rats from each group were divided into two subgroups and given ICV, either ghrelin (G; 1 μg ghrelin/5 μl PBS, n = 7) or solvent alone (5 μl PBS, n = 7) every 24 h for 5 days. The immunohistochemical appearance and quantitative morphology of pituitary ACTH cells were evaluated, as well as peripheral ACTH and corticosterone levels. Central ghrelin administration increased (p < 0.05) ACTH cell volumes in GNF, GFR and GHF rats by 8.1%, 11.8% and 9.1%, respectively, compared to the controls, while significant increases in ACTH cell volume density were observed in GNF and GHF rats. Circulating ACTH and corticosterone levels were elevated (p < 0.05) in GNF and GFR rats by 72.8% and 80.8%, respectively, when compared to the corresponding controls. Thus, central ghrelin administration stimulated the pituitary-adrenal axis under preserved and negative energy balance states.     

Auditory-evoked masseter inhibitory reflex

We aimed to investigate auditory-evoked masseter inhibitory reflex and discuss possible auditory-trigeminal pathways in brainstem. Our study population consisted of 21 healthy volunteers (age-matched 7 males and 14 females). Bilateral electrical blink reflex (BR), auditory blink reflexes (ABR) and electrical MIR (MIR) were studied. After obtaining normal potentials, auditory MIR (AMIR) was studied. Electrical blink reflexes had two components as R1 and R2, and ABR had one evoked potential in all volunteers. There was no significant difference between gender, nor between right- and left-sided BR and ABR. The mean latency of ABR responses were shorter than latencies of R2 phase of BR (p = 0.013 for left-sided responses, p = 0.035 for right-sided responses). Electrical stimulation revealed two suppression periods (SP1 and SP2) in MIR responses bilaterally in all volunteers. Auditory stimulation evoked typical two suppression periods only in 11 subjects (5 males, 6 females). The mean latency of SP1 component of AMIR was significantly longer than those of MIR bilaterally in both males and females, while the SP2 component had a shorter onset. The durations of SP1, SP2 and total SP were always shorter than those obtained in MIR with smaller degree of suppressions. None of the MIR or AMIR responses showed significance difference between sexes. We assume that auditory-evoked MIR might share the similar interneurons as with other electrical or nociceptive stimulation, which connects cochlear-trigeminal neurons via pontine reticular system to premotor area for masseter muscle.     

Effectiveness of individual resource-oriented joint protection education in people with rheumatoid arthritis. A randomized controlled trial

Objective

The modern joint protection (JP) concept for people with rheumatoid arthritis (RA) is an active coping strategy to improve daily tasks and role performance by changing working methods and using assistive devices. Effective group JP education includes psycho-educational interventions. The Pictorial Representation of Illness and Self Measure (PRISM) is an interactive hands-on-tool, assessing (a) the individual's perceived burden of illness and (b) relevant individual resources. Both issues are important for intrinsic motivation to take action and change behaviour. This study compared individual conventional JP education (C-JP) with PRISM-based JP education (PRISM-JP).

Methods

An assessor-blinded multicentre randomized controlled trial, including four JP education sessions over 3 weeks, with assessments at baseline and 3 months.

Results

In total 53 RA patients participated. At 3 months, the PRISM-JP (n = 26) participants did significantly better compared to the C-JP participants (n = 27) in JP behaviour (p = 0.02 and p = 0.008 when corrected for baseline values), Arthritis Self-efficacy (ASES, p = 0.015) and JP self-efficacy (JP-SES, p = 0.047). Within-group analysis also showed less hand pain (p < 0.001) in PRISM-JP group.

Conclusion

PRISM-JP more effectively supported learning of JP methods, with meaningful occupations, resource activation and self-efficacy acting as important mediators.

Practice implications

PRISM improved patient-clinician communication and is feasible for occupational therapy.     

Three questions that patients can ask to improve the quality of information physicians give about treatment options: a cross-over trial

Objective

To test the effect of three questions (what are my options? what are the benefits and harms? and how likely are these?), on information provided by physicians about treatment options.

Methods

We used a cross-over trial using two unannounced standardized patients (SPs) simulating a presentation of mild-moderate depression. One SP was assigned the intervention role (asking the questions), the other the control role. An intervention and control SP visited each physician, order allocated randomly. The study was conducted in family practices in Sydney, Australia, during 2008-09. Data were obtained from consultation audio-recordings. Information about treatment options and patient involvement were analyzed using the Assessing Communication about Evidence and Patient Preferences (ACEPP) tool and the OPTION tool.

Results

Thirty-six SP visits were completed (18 intervention, 18 control). Scores were higher in intervention consultations than controls: ACEPP scores 21.4 vs. 16.6, p < 0.001, difference 4.7 (95% CI 2.3-7.0) and OPTION scores 36 vs. 25, p = 0.001, difference 11.5 (95% CI 5.1-17.8), indicating greater information provision and behavior supporting patient involvement.

Conclusion

Asking these three questions improved information given by family physicians and increased physician facilitation of patient involvement. Practice implications. These questions can drive evidence-based practice, strengthen patient-physician communication, and improve safety and quality.     

Soy extract-dependent changes in morphofunctional parameters of the pituitary corticotropes in adult rats

Numerous studies have established a link between estrogen levels and activity of the hypothalamic pituitary adrenal (HPA) system. Considering the “weak estrogenic” effect of soy isoflavones, this study was designed to evaluate the influence of soy extract treatment on some morphofunctional parameters of rat pituitary corticotropes in vivo. Adult male orchidectomized Wistar rats received estradiol-dipropionate or soy extract in oil/ethanol solvent subcutaneously for 3 weeks. Both controls, sham-operated (So) and orchidectomized (Orx) rats, were injected with solvent, in the same regime. Changes in pituitary volume, total volume, total number and volume of individual corticotropes were evaluated stereologically, while ACTH levels were determined biochemically. In comparison with So rats, estradiol treatment provoked increases (p < 0.05) of: ACTH level (166%), pituitary weight (167%) and volume (102%), total volume (20%) and total number of corticotropes (18%). In comparison to Orx, following estradiol treatment elevation (p < 0.05) of: ACTH level (69%), pituitary weight (131%) and volume (82%), total (30%) and individual volume (29%) of corticotropes was observed. Soy extract treatment led to enhancement (p < 0.05) of: ACTH level (28%), total (25%) and individual volume (20%) of corticotropes. It can be concluded that soy extract acts in a similar way to estradiol, but the increased activity of corticotropes was weaker.     

Haematology patients and the internet – The use of on-line health information and the impact on the patient–doctor relationship

Objective

Patients access on-line health information (OHI) to better understand their health. We aimed to determine which demographic factors influence OHI use. We also explored how OHI is used and subsequent implications to the patient–doctor relationship.

Methods

We distributed a self-administered questionnaire to 202 haematology out-patients.

Results

62.3% used the internet and 54.3% used OHI. Higher education, (P < 0.001, OR 34.62, 95% CI 5.20–230.66) and household incomes of £15 000–25 000 (P = 0.023 OR 4.8 95% CI 1.236–18.59) were positively associated with OHI use.Those reassured after reading OHI had improved trust in their specialist (P < 0.001, OR 52.1, 95% CI 12.3–221.1), improved confidence during consultations, (P < 0.001, OR 23.0, 95% CI 2.8–188.2) and were improved decisions makers (P = 0.008, OR 13.6, 95% CI 4.1–45.7). Those with increased trust in their haematologist also had improved confidence (P < 0.001, OR 6.2, 95% CI 2.2–17.3) and improved decision making ability (P < 0.001, OR 13.6, 95% CI 4.7–39.4). 74.6% of patients did not share OHI with their haematologist.

Conclusions

Two-thirds of participants were exposed directly or indirectly to OHI. OHI affects patients’ view of their health and influences behaviour during consultations.

Practice implications

Haematologists could facilitate patients using OHI by recommending high quality websites and act supportively when patients share OHI.     

Exhaled nitric oxide is associated with acute mountain sickness susceptibility during exposure to normobaric hypoxia

Nitric oxide is a gaseous signaling molecule that participates in a large variety of physiological functions and may have a role in the pathology of altitude illnesses, such as acute mountain sickness (AMS). The effect of normobaric hypoxia on the fraction of exhaled NO (FENO) is a controversial area of high altitude physiology, with the effect varying widely across studies. We exposed 19 male subjects to normobaric hypoxia for 6 h and measured FENO and AMS (via Lake Louise Score) each hour. For data analysis, subjects were divided into AMS-positive and AMS-negative groups based on their Lake Louise Scores during exposure. Eighteen subjects completed the study, and the incidence of AMS was 50%. Mean FENO was unchanged at hour 1 but was significantly elevated above baseline for the remainder of the normobaric hypoxia exposure (p < 0.001). Subjects who developed AMS had a significantly lower mean FENO at baseline compared to resistant subjects (p = 0.013). Further investigations are warranted to confirm our results and to understand the physiological basis of this association.     

Relationship between polysialylated neural cell adhesion molecule and β-endorphin- or gonadotropin releasing hormone-containing neurons during activation of the gonadotrope axis in short daylength in the ewe

Morphological plasticity has been demonstrated between breeding and anestrous seasons in the ewe hypothalamus, particularly for the gonadotropin-releasing hormone (GnRH) system. We sought to determine the impact of a photoperiodic transition, from long days (LD, 16 h light/24 h) to short days (SD; 8 h light/24 h), on the association between a marker of cerebral plasticity, the polysialylated form of neural cell adhesion molecule (PSA-NCAM), and two diencephalic populations: the GnRH and β-endorphin (β-END) neurons, the latter being potent inhibitors of GnRH neuronal activity. We also estimated the number of contacts on GnRH neurons after the passage to SD, using synaptophysin as a marker for synaptic buttons. Those parameters were evaluated in ovariectomized estradiol-replaced ewes using double immunocytochemistry and confocal microscopy at different times after the transition to SD: day 0 (D0), D30, D45, D60 and D112. Luteinizing hormone (LH) secretion was recorded throughout the experiment. High LH levels were observed only at D112. Significantly more PSA-NCAM was found in the GnRH neuron perimeters in the D112 group than in the other groups. This increase was not associated with any change in the number of synaptophysin-immunoreactive contacts on GnRH neurons. The β-END peri-neuronal space was affected negatively by the transition to SD: the percentage of PSA-NCAM on β-END neurons decreased between D45 and D112 in the posterior two thirds of the arcuate nucleus (ARC). These results suggest that photoperiod may reorganize cell interactions in different hypothalamic areas, ultimately reactivating GnRH neurons, in our model of ovariectomized-estradiol replaced ewes.     

Unilateral intra-perilymphatic infusion of substance P enhances ipsilateral vestibulo-ocular reflex gains in the sinusoidal rotation test

Previous studies have reported localization of substance P (SP) within the inner ear and that SP exists abundantly within vestibular endorgans. While SP's functional role in the inner ear remains unclear, SP can act as a neuromodulator in the CNS and directly influences neuronal excitability. We hypothesized that SP might influence neuronal excitability within the vestibular periphery. The present study used the sinusoidal rotation test to investigate the influence of SP after its local application in the guinea pig unilateral inner ear. A tiny hole was made adjacent to the round window in the right ears of Hartley white guinea pigs that had normal tympanic membranes and Preyer reflexes. An osmotic pump infused SP (10⁻⁴ M, 10⁻³ M, and 10⁻² M), neurokinin-1 (NK-1) receptor antagonist (10⁻³ M) alone, or SP (10⁻³ M) + NK-1 receptor antagonist (10⁻³ M) through this hole, with rotation tests performed before, and 12 h and 24 h after the treatment. Results were used to calculate the vestibulo-ocular reflex (VOR) gains. After administration of 10⁻³ M and 10⁻² M SP, significant increases in the VOR gains were noted at 12 h after treatment, with these gains disappearing by 24 h after treatment. This increase was not observed when there was simultaneous NK-1 receptor antagonist administration. There were also no changes in the VOR gains noted after administration of 10⁻⁴ M SP or the NK-1 receptor antagonist alone. These results indicate the possibility that SP may act on vestibular endorgans as an excitatory factor via the NK-1 receptors.     

The effect of GnRH analogues for pituitary suppression on ovarian response in repeated ovarian stimulation cycles

Introduction

Ovarian stimulation is employed in assisted reproduction techniques in order to obtain as many oocytes as possible. The early rise in oestradiol levels may lead to the premature end of the respective cycle. In order to avoid such an effect, pituitary suppression has been employed. The aim of this study was to evaluate whether maintenance or replacement of the type of GnRH analogue (i.e., agonist or antagonist) employed for pituitary suppression in the consecutive intracytoplasmic sperm injection (ICSI) cycle would negatively influence oocyte quality and ICSI outcome.

Material and methods

A retrospective observational study was conducted including 181 women with primary infertility. Patients were divided into four different groups according to the GnRH analogue used for pituitary suppression in the first and consecutive cycle.

Results

When a GnRH agonist was employed for pituitary suppression in the first cycle, the consecutive cycle showed comparable outcomes when performed with either a GnRH agonist or a GnRH antagonist. When the first cycle was performed with a GnRH antagonist, the use of the GnRH agonist in the successive cycle led to an increased number of oocytes retrieved (7.5% vs. 10.3%, p = 0.032) and the production of a higher number of embryos (4.5% vs. 6.3%, p = 0.036).

Conclusions

When the first cycle is carried out with a GnRH antagonist, the use of a GnRH agonist in the successive cycle would lead to increased numbers of oocytes collected and embryos produced.     

IL-1β acutely increases pulmonary SP and permeability without associated changes in airway resistance and ventilation in anesthetized rats

Bronchopulmonary C-fibers (PCFs), when activated, promote substance P (SP) release, increase microvascular leak, and produce bronchoconstriction and apnea. IL-1β administered systemically or locally into the pulmonary parenchyma stimulates PCFs. Thus, we tested whether right atrial bolus injection or aerosol inhalation of IL-1β, to mainly stimulate PCFs, would acutely affect pulmonary SP level and vascular permeability, airway resistance (R_L), and ventilation in anesthetized rats. Our results showed that 30 min after IL-1β injection (2–6 μg kg⁻¹), SP levels and Evans blue extravasation in bronchoalveolar lavage fluid were markedly increased and these responses were eliminated or largely reduced in neonatal capsaicin-treated rats. In contrast, neither injection nor inhalation of IL-1β (5–15 μg ml⁻¹) significantly altered R_L and ventilation. Additionally, the capsaicin-evoked (4 μg kg⁻¹, i.v.) apneic response was unaffected by IL-1β treatment. Our data suggest that IL-1β, as administered in this study, can acutely increase pulmonary SP and vascular permeability, likely via stimulating PCFs, with little impact on R_L and ventilation.     

Menopausal symptoms and associated factors in HIV-positive women

Objective

To evaluate menopausal symptoms and their associated factors in HIV-positive women.

Methods

A cross-sectional study was conducted with 537 women of 40–60 years of age, 273 of whom were HIV-positive and 264 HIV-negative. The women were interviewed to obtain data on their sociodemographic characteristics and menopausal symptoms.

Results

The mean age of the seropositive women was 47.7 ± 5.8 years compared to 49.8 ± 5.3 for the seronegative women (p < 0.001). Bivariate analysis showed a lower prevalence of vasomotor symptoms in the seropositive group (p = 0.009), specifically hot flashes (p < 0.002) and sweating (p = 0.049). Vaginal dryness was also less prevalent in this group (p < 0.005). There were no statistically significant differences between the groups with respect to depression or insomnia. Multiple analysis showed that hot flashes were associated with being peri- or postmenopausal (PR = 2.12; 95%CI: 1.52–2.94). Vaginal dryness was less common in women without a partner (PR = 0.67; 95%CI: 0.49–0.90) and was associated with older age (PR = 1.03; 95%CI: 1.01–1.06) and being in the peri- or postmenopause (PR = 1.69; 95%CI: 1.10–2.60). Depression was inversely associated with being employed (PR = 0.74; 95%CI: 0.58–0.96) and directly associated with the presence of chronic diseases (PR = 1.30; 95%CI: 1.01–1.067). Insomnia was associated with a lower body mass index (PR = 0.96; 95%CI: 0.95–0.97) and with being peri- or postmenopausal (PR = 1.48; 95%CI: 1.11–1.97). No correlation was found between HIV serological status and any of the menopausal symptoms.

Conclusions

In this study, after controlling for confounding variables, HIV infection was not found to be associated with vasomotor, genitourinary or psychological symptoms or with insomnia.     

Can interactive skills-based seminars with standardized patients enhance clinicians’ prevention skills? Measuring the impact of a CME program

Objective

Communication skills are crucial for high-risk behavior screening and counseling. Practicing physicians have limited opportunities to improve these skills. This paper assesses the impact of a continuing medical education (CME) program for Student Health Center clinicians that targeted communication skills, screening practices and patient satisfaction.

Methods

Program evaluation included pre- and post-objective structured clinical examinations (OSCE's), chart review, and provider and patient satisfaction surveys. Data were analyzed using paired t-tests and ranked sum tests.

Results

OSCE scores (n = 15) revealed significant improvements in communication skills overall (p = 0.004) and within specific domains (data gathering: p = 0.003; rapport building: p = 0.01; patient education: p = 0.02), but no change in case-specific knowledge (p = 0.1). Participants (n = 14) reported high satisfaction with program methods (mean = 4.6/5) and content (mean = 4.7/5), 70% planning to alter their clinical practice. Chart audits (pre = 96, post = 103) showed increased screening for smoking (RR 1.65, p = 0.03), depressed mood (RR 1.40, p = 0.04), anhedonia (RR 1.47, p = 0.01), sexual activity (RR 1.73, p = 0.002) and drinking (RR 1.77, p = 0.04). Sampling of satisfaction among participants’ patients (pre n = 689, post n = 383) detected no increase in already high baseline satisfaction.

Conclusion

This curriculum improved clinicians’ relevant skills and screening behavior.

Practice implications

Skills-oriented CME can improve clinicians’ communication skills and screening and counseling practices.     

Effects of morning melatonin administration on electroencephalographic theta to alpha power ratio in reproductive versus postmenopausal healthy female volunteers

Objective: The aim of the present study was to investigate the effect of exogenous morning melatonin administration on the electroencephalogram of reproductive versus postmenopausal women. Methods: Twenty-six female, reproductive and postmenopausal healthy volunteers were randomly assigned to receive melatonin or placebo at 9:00 in the morning. Twelve electroencephalographic recording sessions were performed before the intake of melatonin or placebo and at 15, 30, 45, 60, 75, 90, 120, 150, 180, 240, and 300 min. Theta to alpha ratios for every subject, channel and session were mathematically processed to yield the logarithm (base 10) of the spectral (theta power)/(alpha power) ratio for the 12 electroencephalographic sessions, weighted to the baseline ratio (LwRs). The LwRs were compared between melatonin groups (reproductive versus postmenopausal women) and also between melatonin and control groups. Results: Data from 24 women were analyzed. The LwRs in the reproductive women were significantly lower than the LwRs in postmenopausal women at 60, 180, 240 and 300 min after melatonin consumption (p = 0.007, 0.041, 0.008 and 0.040 respectively). In reproductive women, the LwRs of subjects who received melatonin were significantly lower compared to their controls at 60, 240 and 300 min after melatonin or placebo intake (p = 0.005, 0.006 and 0.019 respectively). In postmenopausal women, no significant differences in the LwRs were calculated for any time point between melatonin and control groups. Conclusions: Our results show that morning melatonin administration produces no electroencephalographic changes in postmenopausal women. In contrast, electroencephalographic changes suggesting a possible awaking effect were observed in reproductive women.     

Implications of MGMT methylation status in pituitary adenoma

Background

Very little literature exists on frequency of MGMT methylation status in pituitary adenoma. We assessed the frequency of MGMT methylation and protein expression in pituitary adenoma and correlated with patients’ age group and prognosis.

Methods

Tumor tissues from 30 patients with pituitary adenoma were evaluated for MGMT promoter methylation status by methylation specific PCR method. All tumors were also immunostained with MIB-1, anti-p53 and anti-MGMT antibodies.

Results

MGMT methylation status was noted in 40% of cases (7/20 non-functioning adenomas and 5/10 functioning adenomas). MGMT protein expression on IHC was noted in 72.2% of unmethylated tumors, while only 41.6% of methylated tumors demonstrated protein expression. The mean labeling index of MGMT protein was higher in unmethylated tumors as compared to the methylated group, though the difference was not statistically significant (18.6% vs 8.8%; p = 0.131). Tumor regrowth occurred in four unmethylated tumors as compared to none in methylated group. Even though there was no correlation between patient age and MGMT methylation status (p = 0.823), we noted that the frequency of methylation in middle age patients (between 30 and 59 yrs) was 64.7%, which was higher compared to other age groups.

Conclusion

This is the first study from India showing MGMT promoter methylation status with protein expression in pituitary adenoma. We noted that tumor regrowth was higher in unmethylated tumors.     

Basking behaviour in relation to energy use and food availability in one of the smallest marsupials

Although several mammals have been observed to bask in the sun, little is known about this behaviour or its energetic consequences. We investigated the importance of basking behaviour for one of the smallest marsupials, Planigale gilesi (9 g). Metabolic rates of captive planigales (n = 6) exposed to simulated natural conditions with access to a radiant heat source were measured. Basking behaviour as a function of food availability was quantified using a video camera installed within the planigales' home cages (n = 7). All planigales basked during respirometry measurements, reducing resting energy expenditure by 58% at an ambient temperature of 15 °C, which reflects conditions in their nesting sites in the wild during winter. Basking behaviour in home cages was displayed by all but one planigale; food withdrawal either triggered basking or it caused a significant increase in basking duration. Our study demonstrates the effectiveness of basking for reducing energy expenditure in one of the smallest marsupials, supporting recent findings on the importance of behavioural thermoregulation in small mammals in general.