Learning-induced enhancement of postsynaptic potentials in pyramidal neurons

We studied the effect of olfactory learning-induced modifications in piriform (olfactory) cortex pyramidal neurons on the propagation of postsynaptic potentials (PSPs). Rats were trained to distinguish between odors in pairs, in an olfactory discrimination task. Three days after training completion, PSPs were evoked in layer II pyramidal cells in piriform cortex brain slices by electrical stimulation of two pathways. Stimulation of layer Ib activated the intra-cortical fibers that terminate on the proximal region of the apical and basal dendrites. Stimulation of layer Ia activated the afferent axons that originate from the olfactory bulb and terminate on the distal apical dendrites. We have previously shown that olfactory training is accompanied by enhanced synaptic transmission in the intrinsic pathway, but not in the afferent pathway at 3 days after training. Here we show that at this stage, in both pathways PSPs evoked in neurons from trained rats had significantly faster rise time measured at the soma compared with PSPs in neurons from pseudo-trained and naive rats. Activation of the slow afterhyperpolarization (AHP), which is generated by potassium channels probably located at the proximal region of both apical and basal dendrites, reduced the amplitude measured at the soma of the proximal intrinsic pathway PSPs more effectively than PSPs that were generated distally by the afferent fibers. Thus the amount of reduction by AHP was used as a measure for the relative distance of PSP-generating sites from the soma. In neurons from trained rats, despite the previously reported reduction in AHP amplitude, AHP conductance shunted the PSPs from both synaptic pathways more efficiently compared with neurons from the control rats. We suggest that in neurons from trained rats PSPs are electrotonicly closer to the soma.     

Pentadecapeptide BPC 157 attenuates disturbances induced by neuroleptics: the effect on catalepsy and gastric ulcers in mice and rats.

A gastric pentadecapeptide, BPC 157, with the amino acid sequence, Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val, MW 1419, known to have a variety of protective effects in gastrointestinal tract and other organs, was recently shown to particularly affect dopamine systems. For instance, it blocks the stereotypy produced acutely by amphetamine in rats, and the development of haloperidol-induced supersensitivity to amphetamine in mice. Consequently, whether pentadecapeptide BPC 157, that by itself has no cataleptogenic effect in normal animals, may attenuate the immediate effects of neuroleptics application, particularly catalepsy, was the focus of the present report. Prominent catalepsy, otherwise consistently seen in the mice treated with haloperidol (0.625, 1.25, 2.5, 5.0 and 10.0 mg/kg b.w., i.p.) and fluphenazine (0.3125, 0.625, 1.25, 2.5 and 5.0 mg/kg b.w., i.p.) after 1.5, 3, 4.5, 6 and 7.5 h following administration, was markedly attenuated when pentadecapeptide BPC 157 (10 microg or 10 ng/kg b.w., i.p.) was coadministered with the neuroleptic. The number of cataleptic mice was markedly lower throughout most of the experimental period. Moreover, on challenge with lower doses of neuroleptics, catalepsy appearance was postponed and the mice, otherwise cataleptic since the earliest period, became cataleptic later, not before 3 or 4.5 h after neuroleptic administration, especially if protected with higher pentadecapeptide dose. Besides catalepsy, coadministration of the pentadecapeptide BPC 157, given in the above mentioned doses, reduced not only catalepsy but somatosensory disorientation (for 7.5 h after administration of a neuroleptic, assessed at intervals of 1.5 h, by a simple scoring system [0-5]) in haloperidol- or fluphenazine-challenged mice as it did in mice treated with sulpiride (20, 40, 80 and 160 mg/kg b.w., i.p.) or with clozapine (25, 50 and 100 mg/kg b.w., i.p.), in which case catalepsy was absent. In other experiments, considering the gastric origin of this pentadecapeptide, the focus was shifted to the evidence that a dose of haloperidol, cataleptogenic due to dopamine receptors blockade, induces gastric ulcers in rats. Coadministration of pentadecapeptide BPC 157 (10 microg, 10 ng, 1.0 ng, 100 pg/kg b.w., i.p.) to rats completely inhibited the lesions otherwise regularly evident 24 h after haloperidol (5.0 mg/kg b.w., i.p.) in control rats (18 of 20 rats had gastric lesions). This activity accompanied the antagonism of the haloperidol catalepsy in rats (assessed at 60-min intervals from I to 5 h after haloperidol), when 10-microg- or 10-ng regimens were given (lower doses could not influence catalepsy). Together, these findings indicate that pentadecapeptide BPC 157 fully interacts with the dopamine system, both centrally and peripherally, or at least, that BPC 157 interferes with some steps involved in catalepsy and/or ulcer formation.     

Progesterone support in IVF: is evidence-based medicine translated to clinical practice? A worldwide web-based survey

This worldwide web-based survey compared the clinical practice for luteal-phase supplementation (LPS) in stimulated IVF cycles to the current evidence-based literature. Eighty-four treatment centres in 35 countries, representing a total of 51,155 IVF cycles/year, responded. Vaginal progesterone alone was used for LPS in 64% of cycles and in another 16% of cycles in combination with either i.m. (15%) or oral progesterone (1%). As a single agent, i.m. progesterone was used in 13% of cycles, oral progesterone in another 2% and human chorionic gonadotrophin (HCG) was still used in 5% of cycles. Progesterone was administered until 10–12 weeks’ gestation in 67% of cycles and in 22% and 12% it was discontinued when fetal heart pulsations are recognized or until βHCG was positive, respectively. In conclusion, in almost two-thirds of the assisted cycles represented in this survey, vaginal administration of progesterone is preferred for LPS. Nevertheless, despite the available literature on the disadvantages of oral progesterone, i.m. progesterone and HCG for LPS, these agents are still used routinely by many practitioners. Furthermore, although there is no firm evidence to support the continuation of LPS until 10–12 weeks’ gestation, this practice is used in the majority of IVF cycles worldwide.This worldwide web-based survey assessed the clinical practice for luteal-phase support in stimulated cycles in comparison to the current evidence-based literature. The survey included the following questions: (i) ‘What is the progesterone you use for luteal support?’; and (ii) ‘How long does progesterone needs to be administered in an IVF cycle if the patient becomes pregnant?’. Eighty-four units from 35 countries representing a total of 51,155 treated IVF cycles/year were included. Vaginal progesterone alone was used for luteal-phase supplementation in 64% of cycles. In another 16% of cycles, vaginal progesterone was used in combination with either intramuscular (15%) or oral progesterone (1%). As a single agent, intramuscular progesterone was used in 13% of cycles, oral progesterone in another 2%, and human chorionic gonadotrophin (HCG) was still used in 5% of cycles. Progesterone was administered until 10–12 weeks’ gestation in 67% of cycles, in 22% of cycles it was discontinued when fetal heart pulsations are recognized, and in 12% it was administered until a positive pregnancy test. In conclusion, in agreement with the currently available literature, in almost two-thirds of assisted cycles worldwide, the vaginal route of progesterone administration is preferred for luteal-phase supplementation. Nevertheless, despite the described disadvantages of oral progesterone, intramuscular progesterone and HCG for LPS, these agents are still used routinely in clinical practice by many practitioners. Furthermore, although there is no firm evidence to support the continuation of LPS until 10–12 weeks of gestation, this practice is used in the majority of IVF cycles worldwide.     

Impact of Margin Assessment Method on Positive Margin Rate and Total Volume Excised

Background

For breast-conserving surgery, the method of margin assessment that most frequently achieves negative margins without increasing the volume of tissue excised is uncertain. We examined our institutional experience with three different margin assessment methods used by six experienced breast surgeons.

Methods

Patients undergoing breast-conserving surgery for invasive carcinoma during July to December of a representative year during which each method was performed (perpendicular, 2003; tangential, 2004; cavity shave, 2011) were included. The effect of margin method on the positive margin rate at first excision and the total volume excised to achieve negative margins were evaluated by multivariable analysis, by surgeon, and by tumor size and presence of extensive intraductal component (EIC).

Results

A total of 555 patients were identified, as follows: perpendicular, 140; tangential, 124; and cavity shave, 291. The tangential method had a higher rate of positive margins at first excision than the perpendicular and cavity-shave methods (49, 15, 11 %, respectively; p < 0.0001). Median volumes to achieve negative margins were similar (55 ml perpendicular; 64 ml tangential; 62 ml cavity shave; p = 0.24). Four of six surgeons had the lowest rate of positive margins with the cavity-shave method, which was significant when compared to the tangential method (p < 0.0001) but not the perpendicular method (p = 0.37). The volume excised by the three methods varied by surgeon (p < 0.0001). The perpendicular method was optimal for T1 tumors without EIC; the cavity-shave method tended to be superior for T2–T3 tumors and/or EIC.

Conclusions

Although the cavity-shave method may decrease the rates of positive margins, its effect on volume is variable among surgeons and may result in an increase in the total volume excised for some surgeons and for small tumors without EIC.     

Interobserver agreement among endoscopists on evaluation of polypoid colorectal lesions visualized with the Pentax i-Scan technique

Background and aimsAdvances in colonoscopy, such as the Pentax i-Scan electronic technique, have the potential to improve the early detection of colorectal cancer. The aim of this multicentre study was to assess the interobserver agreement in the visualization of the surface and margins of colorectal polyps and in distinguishing neoplastic from non-neoplastic polyps.Patients and methodsEight expert endoscopists examined 400 mixed previously recorded images of polyps taken with different Pentax i-Scan settings in order to give an evaluation of the surface of the polyp and regular colonic mucosa, the pit-pattern and the nature of the lesion.ResultsA total of 400 mixed images of polyps with a diameter >5 mm and <10 mm were stored for analysis. Overall, there was a K_f agreement of 0.370 (p < 0.001) and 0.306 (p < 0.001) regarding pit-pattern and margins, respectively. The K_f agreement for the difference between neoplastic and non-neoplastic lesions was of 0.446 (p < 0.001).ConclusionsWe observed good interobserver agreement in the evaluation of neoplastic and non-neoplastic lesions and poor agreement in the evaluation of pit-pattern and margins. Adequate training is required in order to interpret images acquired with the i-Scan technique.     

Partial liberalization of visiting policies and ICU staff: a before-and-after study

Purpose

To investigate possible psychological distress among staff after partial liberalization of visiting policies in intensive care units (ICUs).

Methods

We surveyed eight Italian ICUs planning to increase daily visiting to at least 8 h. Participants completed the Maslach–Jackson Burnout Inventory and the State-Trait Anxiety Inventory before policy change (T0), after 6 months (T1) and 12 months (T2). At T0 and T2, their opinions on the new policy were solicited. Analyses were adjusted for main known confounders (age, gender, centre, educational and marital status, experience in ICU, baseline level of burnout or anxiety, and mortality rate).

Results

Baseline response rate was 89 % (230/258); 198 subjects (77 %) responded at T0 and T2, whereas 184 (71 %) participated in all three phases. High burnout levels were identified in 34.5 % of participants at T0 and 42.6 % at T2 (adjusted p = 0.001). All three phases showed a predominance of high burnout among nurses (adjusted p = 0.002). State and trait anxiety scores remained stable (adjusted p = 0.100 and 0.288, respectively). Most participants viewed the change positively at T0 (doctors 81.7 %; nurses 67.7 %) and T2 (doctors 87.0 %; nurses 62.7 %). At T2, 129 participants made comments (180 positive, 136 negative). Subjects with high burnout were more likely to comment negatively (p = 0.011).

Conclusions

Partial liberalization of ICU visiting policies was associated over the course of a year with a small but significant increase in staff members’ burnout levels. Nonetheless, doctors and nurses viewed the policy positively, maintaining this opinion after 1 year. Negative views were strongly correlated with burnout.     

Antioxidant Activity and Cytotoxicity of the Traditional Indonesian Medicine Tahongai (Kleinhovia hospita L.) Extract

We investigated the leaves of Kleinhovia hospita, a plant which has been traditionally used in Indonesia as phytotherapy to cure liver disease, to describe antioxidant materials from plant sources. K. hospita leaves were extracted with methanol and further partitioned into n-hexane, diethyl ether, and ethyl acetate. The antioxidant activity of each fraction and the residue was assessed using a 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging method and their cytotoxicity on HepG2 liver cancer cells was determined by a MTT assay. The K. hospita leaf methanol extract showed strong antioxidant activity (96%) compared with vitamin C (98%) by the DPPH method and the measured activity from the subsequent extracts of the methanol extract were 48.9% for n-hexane, 74.0% for diethyl ether, 84.3% for ethyl acetate, and 77.1% for the residue. The MTT assay showed the cytotoxicity of the methanol extract on HepG2 cells at 14%, 76%, and 80% at concentrations of 50μg/mL, 87.5μg/mL, and 125μg/mL, respectively. Leaf extracts of the medicinal plant K. hospita showed potent antioxidant activity and moderate cytotoxicity on HepG2 liver cancer cells.