Apoptosis in pulmonary fibrosis: too much or not enough?

Apoptosis plays an important role in both normal lung homeostasis and lung remodeling associated with fibrotic lung disease. Whether apoptosis promotes or inhibits the pathogenesis of pulmonary fibrosis depends upon the cell type involved and the microenvironment of the affected lung. Undue cell loss in the alveolar epithelium may be important early in idiopathic pulmonary fibrosis (IPF) progression, while reduced fibroblast and myofibroblast apoptosis has been associated with the formation of fibrotic lesions. As such, novel therapies based on the stimulation or inhibition of apoptosis may prove beneficial to the treatment of patients with IPF.     

The role of withdrawal in heroin addiction: enhances reward or promotes avoidance?

The compulsive nature of heroin abuse has been attributed to the fact that drug self-administration enables an addict to escape from and avoid the severe withdrawal symptoms resulting from opiate dependence. However, studies of incentive learning under natural motivational states suggest an alternative hypothesis, that withdrawal from heroin functions as a motivational state that enhances the incentive value of the drug, thereby enabling it to function as a much more effective reward for self-administration. In support of this hypothesis, we show here that previous experience with heroin in withdrawal is necessary for subsequent heroin-seeking behavior to be enhanced when dependent rats once again experience withdrawal.     

How much are anesthesiologists exposed to electromagnetic fields in operating rooms?

Numerous electronic devices have been introduced into the operating room. Although little is known about the relationship between exposure to electromagnetic fields (EMF) and health hazards, some authors reported its association with cancer or other diseases. We measured the amount of EMF exposure that an anesthesiologist gets in the operating room. The density of the magnetic field was checked by an extremely low frequency (ELF) field strength measurement system in the 19 operating rooms of our hospital. We measured the magnetic field intensity at a distance of 30 cm, 50 cm, and at the place where the anesthesiologist usually stands from the center of the main monitor. The average exposure quantities of magnetic fields in 19 operating rooms were 2.22 +/- 1.13 mG at 30 cm, 1.29 +/- 0.84 mG at 50 cm and 1.00 +/- 0.78 mG at the anesthesiologist's standing points respectively. Because quantities over 2 or 3 mG were accepted to be high radiation levels of EMF by many reports describing the hazards of EMF, we set 2 mG to be the cutoff value. In some of the 19 operating rooms, the measured EMF density exceeded our cutoff value. Although the health hazards related to EMF exposure are still equivocal, anesthesiologists should consider making an effort to improve their environment and reduce their exposure to EMF.     

Apoptosis or necrosis for tumor immunotherapy: what's in a name?

Here we discuss how the mechanisms by which tumor cells are killed in vivo by gene transfer affects their immunogenicity. Our own work has shown that necrotic cell death induces immunological activation signals which recruit, load, activate and mature appropriate subsets of antigen-presenting cells. In contrast, for apoptotic cell death to be immunogenic, signals additional to cell death alone must be provided within the milieu of the dying tumor. Our conclusion is that the immunogenicity of tumor killing is determined by a combination of factors, including the mechanism of killing, the levels of cell death, the local environment that exists within the dying tumor and, as a result, the nature of the immune/scavenger cells which are present at the time of antigen release. Knowledge of how these factors can influence the immune system and lead to the breaking of tolerance to tumor-associated antigens, can potentially be exploited in the design of effective immunotherapies for cancer using gene transfer.     

Does edema formation occur in the rabbit brain exposed to head-down tilt?

Earlier studies showed that exposure to microgravity caused cephalad fluid shift, increased capillary pressure in the head, and produced facial edema and nasal congestion. In the present study, edema formation in the brain was investigated in rabbits exposed to simulated microgravity, head-down tilt (HDT), by measuring water content and histological examinations. Water content in the brain tissues of rabbits exposed to 2 and 8 days of HDT did not increase significantly compared with that of control animals. Neither vital staining using Evans blue nor immunohistochemical examination demonstrated extravasation of plasma constituents in the brain tissues of the HDT rabbits. Although marked congestion was noted in the brain, hematoxylin and eosin staining did not show edematous changes, such as distension of the perivascular and pericellular spaces and vacuolar appearance, in the tissues obtained from HDT rabbits. Transmission electron microscopy revealed that tight junctions of the capillary endothelium were intact in the HDT rabbits. These results suggest that either HDT up to 8 days does not cause brain edema in rabbits or it induces only a slight brain edema which is hard to be demonstrated by measurement of water content or histological examinations.     

The influence of DHEA pretreatment on prepulse inhibition and the HPA-axis stress response in rat offspring exposed prenatally to polyriboinosinic–polyribocytidylic-acid (PIC)

Prenatal exposure to maternal infection may be associated with the development of neurodevelopmental disorders as well as increased susceptibility to the development of schizophrenia. Prenatal administration of polyriboinosinic–polyribocytidilic-acid, mimicking RNA virus exposure, has been shown to induce schizophrenia-like behavioral, neurochemical and neuorophysiological abnormalities in rodent offspring. In the present study PIC prenatal administration at gestation day 15 was associated with alterations in the acoustic-startle-response/prepulse-inhibition [ASR/PPI] and the HPA-axis stress response in rat offspring on day 90. We show that pretreatment with dehydroepiandrosterone (DHEA) reverses PIC-related ASR/PPI disruption in female rats and normalizes HPA-axis stress response in a united group of male and female rats. Further research in both animal and human studies is recommended in order to confirm these preliminary findings and their application to the understanding and management of schizophrenia and related conditions.     

Withholding breast milk for HIV exposed infants in sub-Saharan Africa: benefit or harm?

Feeding options for HIV exposed infants has remained topical and controversial in most settings of sub-Saharan Africa. This commentary, expresses the author's opinions on this topical issue for and against breastfeeding or infant formula, with supporting evidence drawn from relevant literature on researches conducted in settings of sub-Saharan Africa. At the moment, it seems sensible to recommend that health care workers and policy makers should explore the options of making breastfeeding safer rather than withholding it for sub-Saharan African HIV exposed infants. It is hoped that when Highly Active Antiretroviral Therapy (HAART) becomes universally accessible and available to HIV infected women in sub-Saharan Africa, breast milk HIV transmission will be a rare event and the health benefits of breastfeeding for the infant and mother will be maximized.     

Rats exposed to traumatic stress bury unfamiliar objects--a novel measure of hyper-vigilance in PTSD models?

Electric shocks lead to lasting behavioral deficits in rodents, and as such are often used to model post-traumatic stress disorder (PTSD) in the laboratory. Here we show that a single exposure of rats to 3 mA-strong shocks results in a marked social avoidance that lasts at least 28 days; moreover, the response intensifies over time. In an attempt to study the impact of cue reminders on the behavior of shocked rats, we administered shocks in the presence of a highly conspicuous, 10 cm-large object. This object was introduced into the home cage of rats 28 days after shock exposure. Shocked rats manipulated the object considerably less than controls. More importantly, however, the object was buried by shocked rats. This behavior was virtually absent in controls. The response strongly depended on the intensity of shocks, and was robust. Rats shocked with 3 mA currents spent 40% of time burying the object, which was often hardly visible at the end of the 5 min test. Subsequent experiments demonstrated that the response was not cue-specific as unfamiliar objects were also buried. Rats are well known to bury dangerous objects; the shock-prod burying test of anxiety is based on this response. Behavioral similarities with this test and the differences from the marble-burying behavior of mice suggest that traumatized rats bury unfamiliar objects in defense, and the response can be interpreted as a sign of hyper-vigilance. We further suggest that object burying can be used as a sign of hyper-vigilance in models of PTSD.     

Chorda tympani nerve,may it have a role in stabilizing middle ear pressure?

The chorda tympani (ChT) is a mixed nerve, branch of the facial nerve, crossing the middle ear and containing the preganglionic parasympathetic axons that innervate the sublingual and submandibular glands. The maintenance of a correct middle ear pressure (MEP) is essential for normal ear functions; its regulation has a sophisticated neural control mainly provided by middle ear receptors (tympanic plexus, TP) and Eustachian tube (ET). The information provided by chemoreceptors and baroreceptors of the TP is transmitted to the nuclei of the solitary tract (NST) and then a neural circuit promotes the activation of ET muscles. We hypothesize that the information provided by the TP may modulate submandibular and sublingual glands activity through a neural pathway involving the NST, the superior salivatory nucleus (SSN) and finally the ChT. According to our hypothesis, sudden perturbations of the MEP may stimulate saliva production with consequent swallowing, opening of the Eustachian tube and endotympanic pressure rebalancing.     

N-Cadherin-Mediated Human Granulosa Cell Adhesion Prevents Apoptosis : A Role in Follicular Atresia and Luteolysis?

Studies suggest that cell-cell interactions may regulate apoptosis, and in particular, the calcium-dependent cell adhesion molecule N-cadherin has been shown to be capable of modulating this process. Rat granulosa cells (GCs) are known to express N-cadherin whereas cAMP is known to induce apoptosis in human and rat GCs. Based on these observations, we hypothesized that N-cadherin regulates human GC apoptosis via a cAMP-dependent mechanism. N-cadherin expression was evaluated in ovarian follicles and corpora lutea utilizing immunohistochemical techniques and in luteinized GCs in culture using immunoblotting, flow cytometric analysis, immunohistochemistry, and indirect immunofluorescence techniques utilizing anti-N-cadherin antibodies directed against both the extracellular and cytoplasmic domains of the molecule. Apoptosis was assessed by TUNEL and DNA fragmentation analysis and confirmed by flow cytometric cell cycle analysis and electron microscopy. The rate of GC apoptosis was found to be two- to three-fold lower among aggregated cells, as compared with single cells. N-cadherin was found to be expressed by aggregating GCs in vitro and GCs cultured in the presence of either N-cadherin function disrupting antibodies or peptides exhibiting enhanced rates of apoptosis. GCs in situ stained intensely for N-cadherin in preantral and normal growing preovulatory follicles as well as early corpora lutea. N-cadherin was weak in atretic follicles and regressing corpora lutea. Exposure of GCs to cAMP increased apoptosis while decreasing N-cadherin protein expression in a dose-dependent manner. Cell culture under serum-free conditions increased apoptosis and decreased N-cadherin expression, in part through cleavage of the extracellular domain of the molecule. The metalloproteinase inhibitor 1-10-phenanthroline inhibited the cleavage of the extracellular domain of N-cadherin and concomitantly inhibited the serum-deprivation-induced apoptosis of aggregated GCs. Collectively, these observations suggest that down-regulation of N-cadherin or the absence of a functional extracellular domain of the molecule prevents cell aggregation and is associated with GC apoptosis. In addition, cAMP induces apoptosis in a dose-dependent manner, and this process is dependent, at least in part, on regulation of the N-cadherin molecule at the surface of the cells. We conclude that N-cadherin-mediated GC signaling plays a central role in follicular and luteal cell survival.     

Neural mismatch indices of vowel discrimination in monolingually and bilingually exposed infants: Does attention matter?

Neurophysiological studies of infant speech suggest that mismatch responses (MMRs) have predictive value for later language. Their value, however, is diminished because unexplained differences in the MMR patterns are seen across studies. The current study aimed to identify the functional nature of infant MMRs by recording event-related-potentials (ERPs) to an infrequent English vowel change in internal or final positions of a sequence of ten vowels in six-month-old monolingually and bilingually exposed infants. Increased negativity of the MMR (infrequent minus frequent) was found in final compared to internal positions and correlated with an index of increased attention to the final position. This pattern helps explain the overall greater negativity to the speech sounds in the bilingually exposed female infants. These findings substantially advance our understanding of neural indices of speech perception development and show promise for furthering our understanding of bilingual language development.     

Apoptosis induction by sennoside laxatives in man; escape from a protective mechanism during chronic sennoside use?

Chronic sennoside use induces melanosis coli (MC) and possibly increases colorectal cancer risk. Sennosides alter colonic crypt length, proliferative activity, and bcl-2 expression 18 h after administration. To investigate possible mechanisms for carcinogenesis, the effects of acute sennoside use and the presence of MC on colorectal epithelium were studied. Colorectal biopsies from 15 subjects receiving sennosides 6 h before sigmoidoscopy (Sen), 15 controls (NSen), and 27 with MC [11 moderate (MMC) and 16 severe (SMC)]. were analysed for degree of apoptosis (H&E staining), immunohistochemical p53, p21/WAF and bcl-2 expression, and proliferative activity (labelling index, LI). Apoptosis (p=0.0004), intensity of p53 staining (p=0.01), and p21/WAF expression (p=0.008) were increased in Sen and SMC compared with NSen and MMC. p53 expression was increased in Sen (p=0.004). No difference in bcl-2 expression or LI was observed. Crypts were shorter in Sen (p=0.05) and longer in SMC (p=0.04) than in NSen. It is concluded that sennosides acutely induce apoptosis of colonic epithelial cells, presumably by a p53, p21/WAF-mediated pathway, resulting in shorter crypts. In severe melanosis coli, apoptosis seems to be delayed, causing longer crypts without a rise in proliferative activity or bcl-2 expression. This escape from a presumably protective mechanism may enhance the risk of carcinogenesis during chronic sennoside use.     

Antibiotics may act as growth/obesity promoters in humans as an inadvertent result of antibiotic pollution?

The growth promoting effects of antibiotics were first discovered in the 1940s. Since then, many antimicrobials have been found to improve average daily weight gain and feed efficiency. The total production of antibiotics can be estimated between 100,000-200,000 tons annually and the human population is being influenced, directly or indirectly (from the environment) by this amount of drug. The twentieth-century increase in human height and the obesity of the population is roughly observed since the mass consumption of antibiotics 40-50 years ago. The association between antibiotic consumption and the increase of human growth/obesity is suspected.     

Are there interactional reasons why doctors may find it hard to tell patients that their physical symptoms may have emotional causes? A conversation analytic study in neurology outpatients

Objective

This qualitative study analyses patients’ conversational behaviours to explore whether there are interactional factors that could explain why doctors find clinical encounters in which the diagnosis of functional symptoms (physical symptoms with presumed emotional causes) is explained and psychological treatment offered particularly challenging.

Methods

Twenty out-patient consultations between neurologists and patients with functional symptoms were recorded and analysed using Conversation Analysis. Patients’ communication behaviour was characterised by pervasive interactional resistance. Instances of resistance were identified and counted.

Results

Interactional resistance was especially evident when the aetiology of symptoms and treatment recommendations were discussed. Resistance was expressed overtly (through disagreements, challenges, rejections) or more passively (through moves such as lack of engagement with the interaction, silences or the use of minimal responses).

Conclusion

This study provides objective evidence that doctors face interactional challenges when they try to explain that symptoms are medically unexplained and suggest psychological treatment.

Practice implications

Doctors may try to avoid provoking patients’ overt resistance because they perceive it as unpleasant. However, the display of overt resistance enables them to deal explicitly with the grounds on which patients reject their explanations and recommendations, and to address patients’ particular concerns.