Peptides and proteins with antimicrobial activity

The increase of microbial resistance to antibiotics has led to a continuing search for newer and more effective drugs. Antimicrobial peptides are generally found in animals, plants, and microorganisms and are of great interest to medicine, pharmacology, and the food industry. These peptides are capable of inhibiting pathogenic microorganisms. They can attack parasites, while causing little or no harm to the host cells. The defensins are peptides found in granules in the polymorphonuclear neutrophils (PMNs) and are responsible for the defense of the organism. Several animal defensins, like dermaseptin, antileukoprotease, protegrin, and others, have had their activities and efficacy tested and been shown to be effective against bacteria, fungi, and protists; there are also specific defensins from invertebrates, e.g., drosomycin and heliomicin; from plants, e.g., the types A and B; and the bacteriocins, e.g., acrocin, marcescin, etc. The aim of the present work was to compile a comprehensive bibliographic review of the diverse potentially antimicrobial peptides in an effort to systematize the current knowledge on these substances as a contribution for further researches. The currently available bibliography does not give a holistic approach on this subject. The present work intends to show that the mechanism of defense represented by defensins is promising from the perspective of its application in the treatment of infectious diseases in human, animals and plants.     

The impact of volunteer experience at sport mega‐events on intention to continue volunteering: Multigroup path analysis

This study examined the impacts of volunteers’ motivation and satisfaction through Olympic/Paralympic volunteering experiences on their intention to volunteer for future community events and the moderating role of previous volunteering experience in the relationships among motivations, satisfaction, and intention to continue volunteering. A sample of volunteers (N = 4,824) was drawn from the data collected by Nielsen during the Rio 2016 Olympic and Paralympic Games. Responses from a total of 25 items of volunteer motivations, satisfaction, future intention to volunteer, and previous experience status were used for the study's analyses. Path analysis revealed that among the total sample, motivations had direct and indirect (through satisfaction) effects on intention to volunteer. Results of multigroup path analysis showed that the relationships among motivations, satisfaction, and intention vary by returning and first‐time volunteers, supporting the moderating role of prior volunteering experience in the path model. This study provides a systematic examination of how volunteer motivations and satisfaction may operate differently or similarly between returning and first‐time volunteers.     

Blockage of A2A and A3 adenosine receptors decreases the desensitization of human GABAA receptors microtransplanted to Xenopus oocytes

We previously found that the endogenous anticonvulsant adenosine, acting through A_2A and A₃ adenosine receptors (ARs), alters the stability of currents (I_GABA) generated by GABA_A receptors expressed in the epileptic human mesial temporal lobe (MTLE). Here we examined whether ARs alter the stability (desensitization) of I_GABA expressed in focal cortical dysplasia (FCD) and in periglioma epileptic tissues. The experiments were performed with tissues from 23 patients, using voltage-clamp recordings in Xenopus oocytes microinjected with membranes isolated from human MTLE and FCD tissues or using patch-clamp recordings of pyramidal neurons in epileptic tissue slices. On repetitive activation, the epileptic GABA_A receptors revealed instability, manifested by a large I_GABA rundown, which in most of the oocytes (≈70%) was obviously impaired by the new A_2A antagonists ANR82, ANR94, and ANR152. In most MTLE tissue-microtransplanted oocytes, a new A₃ receptor antagonist (ANR235) significantly improved I_GABA stability. Moreover, patch-clamped pyramidal neurons from human neocortical slices of periglioma epileptic tissues exhibited altered I_GABA rundown on ANR94 treatment. Our findings indicate that antagonizing A_2A and A₃ receptors increases the I_GABA stability in different epileptic tissues and suggest that adenosine derivatives may offer therapeutic opportunities in various forms of human epilepsy.     

Language disturbances as a side effect of prophylactic treatment of migraine

BACKGROUND: Language disturbances have been previously described as word-finding difficulties in epileptic patients. These disturbances have been recently reported in migraineurs in treatment with topiramate but they have never been defined and assessed in these patients with the aid of neuropsychological testing. OBJECTIVE: To verify the occurrence of language disturbances as a side effect of topiramate treatment in episodic and chronic migraine patients. METHODS: Language disturbances were recorded on the basis of spontaneous reports of 30 migraine patients treated with topiramate and 2 control groups (20 patients treated with other prophylactic drugs and 20 patients without prophylactic treatment) and were explored with neuropsychological tests. Psychiatric comorbidity was assessed using Zung Anxiety and Depression Scales. RESULTS: Language disturbances were referred by 26.7% (n=8) of patients during topiramate treatment but by none of the patients in the 2 control groups. All patients in the topiramate group had a worse performance on all tests compared to patients of the 2 control groups. Moreover, in the topiramate group, patients with referred language disturbances had higher scores for all neuropsychological test variables, indicative of a worse performance. Some language functions (Trail Making Tests A and B) seemed to be influenced by the concomitant presence of psychiatric comorbidities, particularly anxiety and depression. CONCLUSION: It can be hypothesized that a disorder such as migraine, which involves numerous cortical and subcortical circuits implicated in the transmission and behavioral and emotional processing of pain, represents a facilitated substrate for the occurrence of language disturbances due to topiramate. This could be the expression of a more generalized impairment of cognitive processing. These aspects should be investigated in prospective studies involving larger migraine patient samples.     

Association between migraine and headache attributed to stroke: a case-control study

Background.— Several studies were carried out to investigate the occurrence of headache attributed to acute stroke in patients with a lifetime history of migraine. Methods.— In a case–control series of 96 acute stroke patients with a lifetime history of migraine (M+) and 96 stroke patients without (M?), ischemic stroke patients only, without secondary infarction, were selected. The headache attributed to acute ischemic stroke was then analyzed. Results.— (M+) patients complained of headache more often than (M?) patients (P < .0001), mainly in the 24 hours before stroke onset (P < .0001). Migraine‐like features of headache were recognized in a greater proportion of cases in the (M+) patient group with ischemic stroke (P < .018). A preferential brainstem location of ischemic stroke in (M+) patients emerged compared with (M?) patients (P = .014). Discussion.— The high prevalence of headache attributed to stroke in (M+) patients, in a relevant proportion of cases presenting as a sentinel headache, suggests that cerebral ischemia lowers the threshold for head pain more easily in these “susceptible” patients. The most frequent involvement of the brainstem in (M+) patients with ischemic infarction concurs with recent reports that emphasized a greater headache frequency when cerebral infarctions are localized in this structure or deep brain gray matter.     

GABA(A)-current rundown of temporal lobe epilepsy is associated with repetitive activation of GABA(A) "phasic" receptors

A study was made of the “rundown” of GABA_A receptors, microtransplanted to Xenopus oocytes from surgically resected brain tissues of patients afflicted with drug-resistant human mesial temporal lobe epilepsy (mTLE). Cell membranes, isolated from mTLE neocortex specimens, were injected into frog oocytes that rapidly incorporated functional GABA_A receptors. Upon repetitive activation with GABA (1 mM), “epileptic” GABA_A receptors exhibited a GABA_A-current (I_GABA) rundown that was significantly enhanced by Zn²⁺ (≤250 μM), and practically abolished by the high-affinity GABA_A receptor inverse agonist SR95531 (gabazine; 2.5–25 μM). Conversely, I_GABA generated by “control” GABA_A receptors microtransplanted from nonepileptic temporal lobe, lesional TLE, or authoptic disease-free tissues remained stable during repetitive stimulation, even in oocytes treated with Zn²⁺. We conclude that rundown of mTLE epileptic receptors depends on the presence of “phasic GABA_A receptors” that have low sensitivity to antagonism by Zn²⁺. Additionally, we found that GABA_A receptors, microtransplanted from the cerebral cortex of adult rats exhibiting recurrent seizures, caused by pilocarpine-induced status epilepticus, showed greater rundown than control tissue, an event also occurring in patch-clamped rat pyramidal neurons. Rundown of epileptic rat receptors resembled that of human mTLE receptors, being enhanced by Zn²⁺ (40 μM) and sensitive to the antiepileptic agent levetiracetam, the neurotrophin brain-derived neurotrophic factor, and the phosphatase blocker okadaic acid. Our findings point to the rundown of GABA_A receptors as a hallmark of TLE and suggest that modulating tonic and phasic mTLE GABA_A receptor activity may represent a useful therapeutic approach to the disease.     

Functional anatomy of cortical areas characterized by Von Economo neurons

Von Economo’s neurons (VENs) are large, bipolar or corkscrew-shaped neurons located in layers III and V of the frontoinsular and the anterior cingulate cortices. VENs are reported to be altered in pathologies such as frontotemporal dementia and autism, in which the individual’s self control is seriously compromised. To investigate the role of VENs in the active human brain, we have explored the functional connectivity of brain areas containing VENs by analyzing resting state functional connectivity (rsFC) in 20 healthy volunteers. Our results show that cortical areas containing VENs form a network of frontoparietal functional connectivity. With the use of fuzzy clustering techniques, we find that this network comprises four sub-networks: the first network cluster resembles a “saliency detection” attentional network, which includes superior frontal cortex (Brodmann’s Area, BA 10), inferior parietal lobe, anterior insula, and dorsal anterior cingulate cortex; the second cluster, part of a “sensory-motor network”, comprises the superior temporal, precentral and postcentral areas; the third cluster consists of frontal ventromedial and ventrodorsal areas constituted by parts of the “anterior default mode network”; and the fourth cluster encompasses dorsal anterior cingulate cortex, dorsomedial prefrontal, and superior frontal (BA 10) areas, resembling the anterior part of the “dorsal attentional network”. Thus, the network that emerges from analyzing functional connectivity among areas that are known to contain VENs is primarily involved in functions of saliency detection and self-regulation. In addition, parts of this network constitute sub-networks that partially overlap with the default mode, the sensory-motor and the dorsal attentional networks.