Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved neuropeptide with well-established neuroprotective actions in the central and peripheral nervous system. Owing to the developmental and functional relationship between the brain and the retina, growing attention has focused on the retinal distribution of PACAP and its receptors, as well as their potential translational relevance. The aim of the present review is to summarize occurrence and distribution of PACAP and its receptors in different vertebrate species.Comparative studies across vertebrates (including fish, birds, rodents, and primates) demonstrate a remarkably conserved retinal expression pattern, particularly for the PAC1 receptor. PACAP signaling components are predominantly localized to the inner retinal layers, with frequent expression in amacrine and bipolar cells and, in some species, Müller glia. Early embryonic expression observed in several species suggests roles in retinal neurogenesis, differentiation, and synaptic maturation, while persistent adult expression supports involvement in synaptic modulation, circadian regulation, and neuronal maintenance.Extensive experimental evidence from rodent models shows that PACAP exerts robust retinoprotective effects in excitotoxic, ischemic, diabetic, and glaucomatous injury paradigms. These protective actions are associated with modulation of pro-survival signaling pathways, attenuation of inflammatory responses, and reduction of apoptotic processes. Importantly, human retinal tissue exhibits comparable localization patterns, and in vitro studies in human-derived retinal cells confirm cytoprotective effects.The evolutionary conservation of retinal PACAP signaling underscores its fundamental physiological importance and supports further investigation of PACAP-based translational strategies for vision-threatening retinal disorders.

Ocular inflammation is a leading cause of visual impairment and blindness worldwide. Systemic bacterial infections can spread hematogenously, resulting in endogenous endophthalmitis. These infections present significant diagnostic and therapeutic challenges due to their systemic origin and involvement of multiple ocular structures such as the retina and cornea. Pituitary adenylate cyclase-activating polypeptide (PACAP), acting through its selective receptor PAC1, exerts potent anti-inflammatory, anti-edema, and regenerative effects in various ocular conditions. This study aimed to assess the protective role of maxadilan, a selective PAC1 receptor agonist, in reducing corneal inflammation in a mouse model of lipopolysaccharide (LPS) -induced ocular inflammation. Mice received systemic LPS injections followed by intravitreal administration of maxadilan. Animals were monitored in vivo using optical coherence tomography (OCT) and tonometry. Post-mortem analyses included evaluation of cytokine expression profiles and routine corneal histological assessment. OCT revealed significantly reduced corneal edema and improved tissue structure with maxadilan administration. Additionally, maxadilan lowered intraocular pressure and reduced inflammatory cell infiltration into the aqueous humor. Cytokine profiling showed decreased expression of critical pro-inflammatory mediators such as GM-CSF, IL-6, MIP-1a, TNF-a, and TREM-1 in the maxadilan-treated group. Histological analyses confirmed that maxadilan preserved normal corneal architecture and effectively prevented pathological keratinization compared to untreated controls. These findings suggest that PAC1 receptor activation has therapeutic potential for controlling inflammation and maintaining corneal health in ocular inflammation.

Background Numerous studies indicate that smoking during pregnancy has harmful effects on the offspring. Prenatal smoke exposure (PSE) may lead to fetal hypoxia and ischemia, which negatively affect brain development and increase the risk of neurological deficits. However, its long‑term impact on retinal vulnerability in adulthood is less well understood.Objective To investigate the effects of prenatal smoke exposure on retinal structure and vulnerability in a chronic retinal hypoperfusion model in adult rats.Methods Wistar rats were mated and exposed to whole‑body tobacco smoke for 2 hours daily from mating until delivery, using a closed‑chamber manual smoking system with four research cigarettes per occasion, modelling passive smoking. Neurobehavioral development was assessed in newborn rats during the first weeks of life. At 5 months of age, permanent bilateral common carotid artery occlusion (BCCAO) was performed under isoflurane anaesthesia via midline neck incision. Two weeks after BCCAO, all animals were sacrificed with an overdose of anaesthetic, and eyes were processed for histological analysis. Retinal layer thickness (outer and inner nuclear and plexiform layers) and cell counts per 100 µm in the ganglion cell layer (GCL) were measured.Results BCCAO resulted in markedly reduced retinal layer thickness and morphological signs of degeneration with individual variation in all layers compared to sham‑operated controls. The number of cells in the GCL decreased by approximately 50%. Prenatal smoke exposure alone also led to a significant reduction in GCL cell number. While our previous work had shown only minor retardation of neurobehavioral development in prenatally smoke‑exposed neonatal rats, the present study demonstrated pronounced histological damage in the retina of adult rats subjected to PSE, with further exacerbation after chronic hypoperfusion.Conclusions Prenatal exposure to tobacco smoke induces long‑lasting structural alterations in the retina and increases susceptibility to later hypoperfusion‑induced retinal injury in adult rats. These findings support the concept that adverse intrauterine exposures have persistent consequences for neural tissues and underscore the importance of avoiding smoking during pregnancy.

(1) Background: Glaucoma is a multifactorial group of diseases characterized by progressive optic neuropathy. Intraocular pressure (IOP) is the only successfully modifiable risk factor for all forms of glaucoma. However, recent research has highlighted the reduction of oxidative stress and neuroinflammation as promising therapeutic targets. In this study, we evaluated the antiglaucomatous effects of a combined herbal extract applied as eye drops in a rat model of glaucoma. (2) Methods: Sprague Dawley rats were divided into four groups: healthy controls, glaucomatous animals treated with preservative-free artificial tears, and healthy and glaucomatous groups receiving combined herbal-based eye drops for 8 weeks. Glaucoma was induced through injection of microbeads into the anterior chamber at week 1 and week 3. Before the first injection and at weeks 4 and 8, rats underwent optical coherence tomography (OCT) and electroretinogram (ERG) recordings. Retinal analyses were conducted to assess retinal ganglion cell (RGC) count, vessel density, and markers of neural pathways, oxidative stress, and inflammation. (3) Results: The combination of herbal extracts showed beneficial effects on IOP elevation, and significantly improved ERG responses. Neuroprotective effects were assessed using OCT, immunohistochemistry, and proteomics. Most parameters in herbal eye drop-treated rats were not statistically different from those in healthy controls. (4) Conclusions: Topical administration of plant-based compounds may serve as an effective supportive therapy for ocular hypertension and retinal neuroprotection.

The continuously growing diabetes population is a significant concern with type 2 diabetic retinal disease (T2DRD), which is a leading cause of permanent blindness. However, the underlying pathophysiological mechanism of T2DRD has not yet been fully understood. Pituitary adenylate cyclase-activating polypeptide (PACAP) was first isolated from the ovine hypothalamus based on its stimulating effect on the adenylate cyclase enzyme in anterior pituitary cells. PACAP38 (PACAP with 38 amino acids) activates anti-apoptotic pathways, inhibits pro-apoptotic signaling, and creates an anti-inflammatory environment in the retina. The aim of the present study was to test the possible retinoprotective effect of the topical administration of PACAP38 in a type 2 diabetic animal model induced by a high-fat diet and the intraperitoneally injected low-dose streptozotocin (STZ). Wistar rats were divided into four groups: the control, control + PACAP38, diabetes, and diabetes + PACAP38 groups randomly. Type 2 diabetes was induced with the combination of STZ (30 mg/kg) and a high-fat diet. All rats were treated topically two times a day for 16 weeks: the control + PACAP38 and diabetes + PACAP38 groups were applied with PACAP38 eye drops (1 µg/drop), while the control and diabetes groups were administered using vehicles (artificial tears). The diabetes model was validated by a fasting oral glucose tolerance test (OGTT) and C-peptide ELISA test. Animals were monitored during the whole experiment for the progression of the disease using electroretinography (ERG) and optical coherence tomography (OCT). Post-mortem immunohistochemistry and a vessel analysis were performed in the retina samples after 16 weeks. An OGTT, a C-peptide ELISA test, and the investigation of blood parameters proved the development of type 2 diabetes. Significant differences could be detected in visual function between the two diabetic groups at week 16 (in the a-wave, b-wave, and OP amplitudes), where the diabetes PACAP38-treated group was similar to the control ones. OCT measurements correlated with ERG data, where the total retinal thickness was preserved in the diabetes + PACAP38 group. PACAP38 also protected the microvascular structure in the retina. Topically administered PACAP38 has potent neuroprotective effects against type 2 diabetic retinal disease; therefore, it could be a promising therapeutic approach for the treatment of T2DRD.

The prevalence of hypoxia-caused eye diseases is increasing, but effective, non-invasive treatment options are not available. Abscisic acid (ABA) is a plant hormone with anti-inflammatory and antioxidant effects. ABA is also present in various mammalian tissues and plays an important role in metabolic processes. Therefore, we aimed to investigate the potential protective role of ABA eye drops in ischemic retinopathy. Retinal ischemia was induced by permanent unilateral common carotid artery occlusion (UCCAO) in mice. Half of the animals received ABA eye drops two times a day for two weeks. Optical coherence tomography (OCT) was used to follow the changes in retinal thickness. Moreover, immunohistochemistry and molecular biology methods were used to explore the morphological changes and the underlying mechanisms, respectively. Based on OCT measurements, ischemic retinopathy was successfully developed. The decrease in the thickness of numerous retinal layers could be prevented with ABA eye drops. The ganglion cell number decreased significantly after UCCAO in the central and peripheral regions of the retina. ABA treatment could moderate the damage in both regions. Furthermore, our apoptosis array results suggest that ABA regulates the apoptotic pathways under hypoxic conditions. In conclusion, ABA eye drops may represent a new potential therapeutic option for the treatment of ischemic retinopathy.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide exerting, among others, strong trophic and protective effects. It plays a role in several physiological functions, including glucose homeostasis. The protective effects of PACAP are mainly mediated via its specific PAC1 receptor by stimulating anti-inflammatory, anti-apoptotic and antioxidant pathways. The aim of the present review is to summarize data on the protective effects of PACAP in the three major complications of diabetes, retinopathy, nephropathy and neuropathy, as well as some other complications. In type 1 and type 2 diabetic retinopathy models and in glucose-exposed cells of the eye, PACAP counteracted the degeneration of retinal layers and inhibited apoptosis and factors leading to abnormal vessel growth. In models of nephropathy, kidney morphology was better retained after PACAP administration, with decreased apoptosis and fibrosis. In diabetic neuropathy, PACAP protected against axonal–myelin lesions and less activation in pain processing centers. This neuropeptide has several other beneficial effects in diabetes-induced complications like altered vascular response, cognitive deficits and atherosclerosis. The promising therapeutic effects of PACAP in several pathological conditions have encouraged researchers to design PACAP-related drugs and to develop ways to enhance tissue delivery. These intentions are expected to result in overcoming the hurdles preventing PACAP from being introduced into therapeutic treatments, including diabetes-related conditions.

A hipofízis adenilát-cikláz-aktiváló polipeptid (PACAP) egy 27 vagy 38 aminosavból álló neuropeptid széles körű előfordulással és hatásokkal. Többek között megtalálható a hasnyálmirigy endokrin szigeteiben, és részt vesz a cukorháztartás szabályozásában. A peptid egyik legtöbbet tanulmányozott hatása az erőteljes sejtvédő hatás, mely elsősorban a specifikus PAC-1 receptorokon keresztül valósul meg az apoptotikus, gyulladásos és oxidatív stressz útvonalak gátlásával. A jelen tanulmányunk célja a PACAP diabéteszes szövődményekben kimutatott jótékony hatásainak összefoglalása, elsősorban a retinopátia‑, nefropátia- és neuropátia-modelleken talált eredmények bemutatásával. A PACAP 1-es és 2-es típusú diabétesz modelljében is védő hatást fejt ki a retinán, valamint csökkenti a szaruhártya károsodását diabéteszes keratopátia modelljében. Nefropátiában a PACAP-kezelt állatokban a vese szöveti szerkezete megőrzött maradt, csökkent gyulladásos, apoptotikus és fibrotikus jelekkel. A PACAP részt vesz az idegi regeneráció szabályozásában is, amit diabéteszes neuropátiában is kimutattak. A kezelés védte az idegeket az axon- és mielinkárosodással szemben, valamint csökkent volt a fájdalomközpontok krónikus aktivációja a központi idegrendszerben. A PACAP további jótékony hatásokat mutatott diabéteszben megfigyelt kóros érelváltozásokban, kognitív hanyatlásban és ateroszklerózisban. A peptid potenciális hatásai remélhetőleg terápiás felhasználásra kerülhetnek a jövőben. Mivel a PACAP-ot is a dipeptidil-peptidáz-4 bontja, az inhibitorokat szedő betegekben a megemelkedett PACAP-szint is hozzájárulhat a DPP-4 enzimet gátlók számos védő hatásához.

Diabetic cardiomyopathy (DbCM) is a chronic metabolic disorder with few effective treatment strategies. Our previous study demonstrated that activated protein C (aPC), a serine protease, exerts cytoprotective effects in DbCM. However, the mechanisms underlying its role in DbCM require further elucidation. We developed a type 1 diabetic mouse model using thrombomodulin gene point mutation mice (TMP/P) with reduced endogenous aPC generation and investigated the protective effects of aPC on DbCM through intraperitoneal injection of protein C (PC). Myocardial functions and structure were assessed by echocardiography and histology. Transcriptomic analysis and immunological evaluation were conducted to investigate the downstream targets. The anti-senescence role of aPC was reaffirmed by PC treatment in vivo and aPC intervention in cultured neonatal rat ventricular myocytes in vitro. Endogenous aPC levels were reduced and positively correlated with cardiac diastolic function in diabetic mice. Cardiomyocytes manifested a senescent phenotype in DbCM. With impaired aPC activation, TMP/P mice exhibited aggravated diabetes-induced cardiac dysfunction and cardiomyocyte senescence. Mechanistically, aPC alleviated cardiomyocyte senescence in DbCM by acting on PAR1/PAR3 receptors to restore the interaction between P85 and CaMKIIδ, thereby inhibiting CaMKIIδ phosphorylation and its nuclear translocation. In summary, our study highlights that aPC ameliorates cardiomyocyte senescence in DbCM via PAR1/PAR3-P85-CaMKIIδ axis.

Kettlebell as a sport has gained recognition worldwide. We characterized the physiological responses induced by a simulated kettlebell competition routine in experienced kettlebell athletes (n = 26) in a two-group, pre-post plus short-term follow-up, non-randomized experiment. The experimental group (EXP) included 13 kettlebell athletes, while the control group (CON) consisted of 13 individuals with prior recreational exposure to kettlebell activities. EXP performed a 10-minute-long, long-cycle kettlebell routine, whereas CON engaged in seated rest. Cardiovascular and neuromuscular outcomes were measured at rest, after warm-up, during exercise, at 0 (immediately post), 5 and 15 min into recovery. Group-by-time interactions revealed that the 10-minute-long, long-cycle kettlebell routine increased (P < 0.05) the levels of all outcomes (e.g. heart rate, blood pressure, blood lactate) (range of effect sizes: -0.9-8.9) with many outcomes remaining well above baseline at 5 and 15 min into recovery. A notable exception was a lack of change in maximal squat strength. Kettlebell experience and mass correlated with changes in oxygen uptake (Delta VO2) and in ventilation (Delta VT) (r = -0.70, 0.64, -0.87, and 0.73, respectively, P < 0.05) in EXP. Kettlebell routine evoked significant changes in all physiological variables (respiratory and cardiovascular), out of which the heart rate (HR), diastolic blood pressure (DBP), rate pressure product (RPP), and blood lactate (BL) outlasted the routine for at least 15 min. Future studies should longitudinally examine physiological responses to kettlebell training throughout a season. Long-cycle kettlebell routine adds to the repertoire of evidence-based exercise options for high-intensity exercise.

Retinoblastoma represents the most prevalent malignant neoplasm affecting the eyes in childhood. The clear-cut origin of retinoblastoma has not yet been determined; however, based on experiments, it has been suggested that RB1 loss in cone photoreceptors causes retinoblastoma. Pituitary adenylate-cyclase activating polypeptide (PACAP) is a pleiotropic neuropeptide which has been shown to be affected in certain tumorous transformations, such as breast, lung, kidney, pancreatic, colon, and endocrine cancers. This study aimed to investigate potential changes in both PACAP38 and PAC1 receptor (PAC1R) expression in human retinoblastoma and the effect of PACAP38 administration on the survival of a human retinoblastoma cell line (Y-79). We analyzed human enucleation specimens removed because of retinoblastoma for PACAP38 and PAC1R immunostaining and the effect of PACAP38 on the survival of the Y-79 cell line. We described for the first time that human retinoblastoma cells from patients showed only perinuclear, dot-like immunopositivity for both PACAP38 and PAC1R, irrespective of laterality, genetic background, or histopathological features. Nanomolar (100 nM and 500 nM) PACAP38 concentrations had no effect on the viability of Y-79 cells, while micromolar (2 µM and 6 µM) PACAP38 significantly decreased tumor cell viability. These findings, along with general observations from animal studies showing that PACAP38 has strong anti-apoptotic, anti-inflammatory, and antioxidant effects on ocular tissues, together suggest that PACAP38 and its analogs are promising candidates in retinoblastoma therapy.

Introduction: The COVID-19 pandemic prompted prolonged lockdowns in Jordan and Hungary from March 2020, aiming to curb the virus's spread. Due to distinct cultural backgrounds, this study explores variations in the impact of confinement on female workers in both countries. Aims: Through a questionnaire survey, the research examines pre, during, and post-lockdown habits of female employees, encompassing work patterns, diet, physical activity, and family responsibilities, aiming to identify cultural differences. Results: Notable differences emerged in lockdown homework engagement (62% Hungary, 81% Jordan), remote work intensity (40% Hungary, 83% Jordan), and partner-shared responsibilities. Hungarian women exhibited higher physical activity levels and fewer changes in eating habits, with only 28% reporting weight gain, in contrast to 67% of Jordanian women. The average body mass index for Hungarians is 25.1 ± 4.8 kg/m2, while Jordanians have 21.6 ± 3.0 kg/m2. Conclusion: The study underscores the role of physical activity in overcoming pandemic challenges. Promoting regular exercise for women in both countries is crucial, requiring enhanced motivation and opportunities, even amid potential future epidemics.

The retina is one of the highest metabolically active tissues with a high oxygen consumption, so insufficient blood supply leads to visual impairment. The incidence of related conditions is increasing; however, no effective treatment without side effects is available. Furthermore, the pathomechanism of these diseases is not fully understood. Our aim was to develop an optimal ischemic retinopathy mouse model to investigate the retinal damage in a time-dependent manner. Retinal ischemia was induced by bilateral common carotid artery occlusion (BCCAO) for 10, 13, 15 or 20 min, or by right permanent unilateral common carotid artery occlusion (UCCAO). Optical coherence tomography was used to follow the changes in retinal thickness 3, 7, 14, 21 and 28 days after surgery. The number of ganglion cells was evaluated in the central and peripheral regions on whole-mount retina preparations. Expression of glial fibrillary acidic protein (GFAP) was analyzed with immunohistochemistry and Western blot. Retinal degeneration and ganglion cell loss was observed in multiple groups. Our results suggest that the 20 min BCCAO is a good model to investigate the consequences of ischemia and reperfusion in the retina in a time-dependent manner, while the UCCAO causes more severe damage in a short time, so it can be used for testing new drugs.

Despite the high probability of glaucoma-related blindness, its cause is not fully understood and there is no efficient therapeutic strategy for neuroprotection. Vascular factors have been suggested to play an important role in glaucoma development and progression. Previously, we have proven the neuroprotective effects of pituitary adenylate-cyclase-activating polypeptide (PACAP) eye drops in an inducible, microbeads model in rats that is able to reproduce many clinically relevant features of human glaucoma. In the present study, we examined the potential protective effects of PACAP1-38 on the retinal vasculature and the molecular changes in hypoxia. Ocular hypertension was induced by injection of microbeads into the anterior chamber, while control rats received PBS. PACAP dissolved in vehicle (1 µg/drop) or vehicle treatment was started one day after the injections for four weeks three times a day. Retinal degeneration was assessed with optical coherence tomography (OCT), and vascular and molecular changes were assessed by immunofluorescence labeling. HIF1-α and VEGF-A protein levels were measured by Western blot. OCT images proved severe retinal degeneration in the glaucomatous group, while PACAP1-38 eye drops had a retinoprotective effect. Vascular parameters were deteriorated and molecular analysis suggested hypoxic conditions in glaucoma. PACAP treatment exerted a positive effect against these alterations. In summary, PACAP could prevent the severe damage to the retina and its vasculature induced by ocular hypertension in a microbeads model.

(1) The unilateral countermovement jump is commonly used to examine frontal plane kinetics during unilateral loading and to identify athletes with an increased risk of lower limb injuries. In the present study, we examined the biomechanical mechanisms of knee and pelvis stabilization during unilateral vertical jumps. (2) Healthy males performed jumps on a force plate with the dominant leg. Activity of the dominant-side gluteus medius and the contralateral-side quadratus lumborum and erector spinae muscles was recorded with surface EMG. The EMG data were normalized to the EMG activity recorded during maximal voluntary isometric hip abduction and lateral trunk flexion contractions. During jumps, the propulsive impulse was measured, and the pelvis and thigh segmental orientation angles in the frontal plane were recorded and synchronized with the EMG data. (3) The magnitude of knee valgus during the jump did not correlate with hip abduction force, but negatively correlated with gluteus medius activity. This correlation became stronger when gluteus medius activity was normalized to hip abduction force. Propulsive impulse did not correlate with any neuromechanical measurement. (4) We conclude that hip abduction force itself does not regulate the magnitude of knee valgus during unilateral jumps; rather, the gluteus medius should be highly activated to increase frontal-plane knee joint stability.

Studies have proven the effectiveness of different weight-bearing exercise interventions for diabetic patients with neuropathy; however, several adverse effects were reported using solid surfaces. Thus, in the present study, we investigated the effects of a novel sand exercise training intervention on biomechanical and functional parameters in seven diabetic patients (age = 62.7 ± 9.7 years) with neuropathy. Patients underwent a 12-week sand exercise training program, using strengthening, stretching, balance, and gait exercises. They were tested for ankle plantar- and dorsiflexion peak torque, active range of motion (ROM), timed up and go (TUG), and bilateral static balance. EMG activity of tibialis anterior (TA), gastrocnemius medialis (GM), and lateralis (GL) muscles were measured during unilateral isometric contraction in plantar- and dorsiflexion. In the intervention period, plantarflexion peak torque improved significantly (p = 0.033), while dorsiflexion torque remained unchanged. Plantar- and dorsiflexion ROM increased (p = 0.032) and (p = 0.021), respectively. EMG activity of GM (p = 0.005) and GL (p = 0.002) measured during dorsiflexion and postural sway in the balance test, as well as time to complete the TUG test, decreased significantly (p = 0.021) and (p = 0.002), respectively. No adverse effect was reported during the intervention period. We concluded that sand exercise training can be a safe and effective method to improve plantarflexion strength, ankle flexibility, and balance, which is reflected in better gait function in patients with diabetic peripheral neuropathy (DPN).

Corneal epithelium responds to insults with a rapid wound healing, which is essential for maintaining vision. The proper balance of apoptotic and proliferation-stimulating pathways is critical for normal regeneration. Pituitary adenylate cyclase activating polypeptide (PACAP) is an important growth factor during the development of the nervous system and exerts cytoprotective effects in injuries. The aim of the present study was to investigate the effects of PACAP on corneal epithelial wound healing in rats and on two important protective signaling molecules, Akt and ERK1/2, both of which have been reported to play important roles during cell survival and regeneration, including corneal wound healing. Wistar rats received PACAP treatment in form of eyedrops, containing 1, 5 and 10 µg PACAP27, immediately and every two hours after corneal abrasion. Corneas were stained with fluorescein dye and further processed for histological staining or Western blot analysis for Akt and ERK1/2 expression. Our results showed that topical PACAP application enhanced corneal wound healing, as the area of injury was significantly less in PACAP-treated groups. Furthermore, both ERK1/2 and Akt signaling was induced upon PACAP administration in both injured and intact corneas. In summary, the present results show that PACAP enhances corneal wound healing in a rat model of corneal abrasion.

Aim The aim of the study was to investigate acute and chronic effects of a two-week eccentric concentric, dynamometric training concerning the time-course changes of blood antioxidant parameters (total antioxidant capacity, catalase enzyme activity, thiol concentration), and to compare the adaptability of young and older muscle to this type of training. Methods Seventeen moderately trained young and older men participated in this research. Subjects performed six eccentric concentric exercise bouts during the training period and maximal voluntary isometric contraction torque, plasma CK and intensity of muscle soreness were determined before and 24 h after the first exercise. During five testing sessions (baseline, 24 h, 48 h, week 1, week 2) the level of blood antioxidants were measured. Results No significant changes were registered in total antioxidant capacity and catalase enzyme activity for any time points; furthermore, no difference was found between groups during the training period. However, total thiol concentrations measured two weeks after the first exercise bout significantly differed between the young and elderly groups. Plasma CK and the subjective intensity of soreness elevated significantly 24 h following the first training, while maximal voluntary isometric contraction torque decreased at the same time. Conclusions Our results do not support previous findings that chronic, short-term eccentric concentric training programs enhance the antioxidant defense of well-trained older and young men. This type and setting of exercise did not cause a different time course of changes in the markers of exercise-induced muscle damage (EIMD) in the studied population. Subjects may already have adapted to maintain constant levels of antioxidants and isometric torque due to their active lifestyle.

Songorine (SON) is a diterpenoid alkaloid from Aconitum plants. Preparations of Aconitum roots have been employed in traditional oriental herbal medicine, however, their mechanisms of action are still unclear. Since GABA-receptors are possible brain targets of SON, we investigated which subtypes of GABA-receptors contribute to the effects of SON, and how SON affects anxiety-like trait behavior and psychomotor cognitive performance of rats. First, we investigated the effects of microiontophoretically applied SON alone and combined with GABA-receptor agents picrotoxin and saclofen on neuronal firing activity in various brain areas. Next, putative anxiolytic effects of SON (1.0-3.0 mg/kg) were tested against the GABA-receptor positive allosteric modulator reference compound diazepam (1.0-5.0 mg/kg) in the elevated zero maze (EOM). Furthermore, basic cognitive effects were assessed in a rodent version of the psychomotor vigilance task (PVT). Local application of SON predominantly inhibited the firing activity of neurons. This inhibitory effect of SON was successfully blocked by GABA(A)-receptor antagonist picrotoxin but not by GABA(B)-receptor antagonist saclofen. Similar to GABA(A)-receptor positive allosteric modulator diazepam, SON increased the time spent by animals in the open quadrants of the EOM without any signs of adverse psychomotor and cognitive effects observed in the PVT. We showed that, under in vivo conditions, SON acts as a potent GABA(A)-receptor agonist and effectively decreases anxiety without observable side effects. The present findings facilitate the deeper understanding of the mechanism of action and the widespread pharmacological use of diterpene alkaloids in various CNS indications.

Pituitary adenylate cyclase–activating polypeptide (PACAP) is a neuropeptide with widespread distribution and diverse biological functions. Several studies show that PACAP has strong cytoprotective effects mediated mostly through its specific PAC1 receptor (PAC1-R) and it plays important roles in several pathological conditions. Its distribution and altered expression are known in various human tissues, but there is no descriptive data about PACAP and its receptors in the human eyebulb. Since PACAP38 is the dominant form of the naturally occurring PACAP, our aim was to investigate the distribution of PACAP38-like immunoreactivity in the human eye and to describe the presence of PAC1-R. Semiquantitative evaluation was performed after routine histology and immunohistochemical labeling on human eye sections. Our results showed high level of immunopositivity in the corneal epithelium and endothelium. Within the vascular layer, the iris and the ciliary body had strong immunopositivity for both PACAP and PAC1-R. Several layers of the retina showed immunoreactivity for PACAP and PAC1-R, but the ganglion cell layer had a special pattern in the immunolabeling. Labeling was observed in the neuropil within the optic nerve in both cases and glial cells displayed immunoreactivity for PAC1-R. In summary, our study indicates the widespread occurrence of PACAP and its specific receptor in the human eye, implying that the results from in vitro and animal studies have translational value and most probably are also present in the human eye.