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The aim of this study is to investigate the healing and prophylactic effect of drying-off antibiotic therapy using the selective and non-selective approach of administration of the antibiotics. First experimental group at the start of the dry period were treated non-selectively (all halves) intracisternally with antibiotics. In the second group, we only treated those halves that were diagnosed with subclinical mastitis. The control group of 9 goats was not treated. The number of somatic cells in treated groups after birth decreased from 2586 x 10³/ mL to 560 x 10³/mL in the first group and from 1978 x 10³/mL to 526 x 10³/mL in the second. Post partum, 10% of the halves were found to have subclinical mastitis. A healing effect was achieved in 25% (n=5) milk halves. New intramammary infections developed during the dry period also occurred in 5% (n=1) of the milk halves. In the second post-partum study, subclinical mastitis was observed only in 5% (n=1). Healing was achieved in 30% (n = 6) and the new intramammary infections (NIMIs) were 10% (n=2). In the control group, healing was only observed in 5% (n=1) and NIMI were 27.78% (n=5). The application of both treatment approaches, results in reduction in prevalence and manifestation of mastitis, as well as reduction of somatic cells in milk after kidding. The selective treatment method may be preferred, in order to reduce the cost of medications in conducting treatment and prophylaxis programs. [ABSTRACT FROM AUTHOR]

Nano solutions are widely used in medicine and also have the potential to be used when performing allelopathy screening studies. The present experiment aimed to test the effectiveness of colloidal nano silver Silver-Amber© with nanoparticles of 20 nm (>20 mg/L at a purity level of 99.99%) as a carrier of allelochemicals in laboratory conditions. The influence of eleven concentrations of Silver-Amber© (0.10, 0.20, 0.39, 0.78, 1.56, 3.13, 6.25, 12.5, 25.0, 50.0 and 100.0% v / v ) on the germination and initial development of test plant Lactuca sativa L. in 0.75% agar medium was studied. Data revealed that when increasing the quantitative ratio of Silver-Amber©, an inhibitory effect on seed germination (from 37.8 to 94.3%) and on the plant growth (from 54.0 to 98.9%) appeared. Lower concentrations (0.63 to 0.04 ppm) had an indifferent to statistically unproven stimulatory effect on the germination and initial development of L. sativa (GI ranged from 88.7-94.6%). Therefore, nano silver can be used as carrier of allelochemicals in allelopathic studies in laboratory conditions.

Introduction: Implicated in both aging and Alzheimer's disease (AD), mammalian target of rapamycin (mTOR) is overactive in AD brain and lymphocytes. Stimulated by growth factors such as insulin, mTOR monitors cell health and nutrient needs. A small molecule oral drug candidate for AD, simufilam targets an altered conformation of the scaffolding protein filamin A (FLNA) found in AD brain and lymphocytes that induces aberrant FLNA interactions leading to AD neuropathology. Simufilam restores FLNA's normal shape to disrupt its AD-associated protein interactions. Methods: We measured mTOR and its response to insulin in lymphocytes of AD patients before and after oral simufilam compared to healthy control lymphocytes. Results: mTOR was overactive and its response to insulin reduced in lymphocytes from AD versus healthy control subjects, illustrating another aspect of insulin resistance in AD. After oral simufilam, lymphocytes showed normalized basal mTOR activity and improved insulin-evoked mTOR activation in mTOR complex 1, complex 2, and upstream and downstream signaling components (Akt, p70S6K and phosphorylated Rictor). Suggesting mechanism, we showed that FLNA interacts with the insulin receptor until dissociation by insulin, but this linkage was elevated and its dissociation impaired in AD lymphocytes. Simufilam improved the insulin-mediated dissociation. Additionally, FLNA's interaction with Phosphatase and Tensin Homolog deleted on Chromosome 10 (PTEN), a negative regulator of mTOR, was reduced in AD lymphocytes and improved by simufilam. Discussion: Reducing mTOR's basal overactivity and its resistance to insulin represents another mechanism of simufilam to counteract aging and AD pathology. Simufilam is currently in Phase 3 clinical trials for AD dementia., Competing Interests: This basic research was supported in part by supplies and funding from Cassava Sciences, Inc. LB is an employee and shareholder of Cassava Sciences, as was the late NF. H-YW is an employee of City University of New York School of Medicine, is a long-time consultant and scientific advisor to Cassava Sciences, owns an insignificant financial interest (less than ½ of 1%) in the equity of Cassava Sciences, and has consulted to various pharmaceutical companies over the past 20 years. LB and H-YW are inventors on simufilam patents. None of the authors are due patent royalties. This basic research was conducted in non-GCP compliant facilities. ZP and K-CL are employees of City University of New York School of Medicine. BN, TD, and JP are investigators in the clinical trial protocols. Author BN is employed by IMIC, Inc. Authors TD and JP are employed by Cognitive Clinical Trials., (Copyright © 2023 Wang, Pei, Lee, Nikolov, Doehner, Puente, Friedmann and Burns.)

Advanced in the present paper is an innovative approach for three-dimensional modeling of the regular relief topography formed via a ball burnishing process. The proposed methodology involves capturing a greyscale image of and profile measuring the surface topography in two perpendicular directions using a stylus method. A specially developed algorithm further identifies the best match between the measured profile segment and a row or column from the captured topography image by carrying out a signal correlation assessment based on an appropriate similarity metric. To ensure accurate scaling, the image pixel grey levels are scaled with a factor calculated as being the larger ratio between the ultimate heights of the measured profilograms and the more perfectly matched image row/column. Nine different similarity metrics were tested to determine the best performing model. The developed approach was evaluated for eight distinct types of fully and partially regular reliefs, and the results reveal that the best-scaled 3D topography models are produced for the fully regular reliefs with much greater heights. Following a thorough analysis of the results obtained, at the end of the paper, we draw some conclusions and discuss potential future work.

Importance: One major advantage of developing large, federally funded networks for clinical research in neurology is the ability to have a trial-ready network that can efficiently conduct scientifically rigorous projects to improve the health of people with neurologic disorders., Observations: National Institute of Neurological Disorders and Stroke Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) was established in 2011 and renewed in 2018 with the goal of being an efficient network to test between 5 and 7 promising new agents in phase II clinical trials. A clinical coordinating center, data coordinating center, and 25 sites were competitively chosen. Common infrastructure was developed to accelerate timelines for clinical trials, including central institutional review board (a first for the National Institute of Neurological Disorders and Stroke), master clinical trial agreements, the use of common data elements, and experienced research sites and coordination centers. During the first 7 years, the network exceeded the goal of conducting 5 to 7 studies, with 9 funded. High interest was evident by receipt of 148 initial applications for potential studies in various neurologic disorders. Across the first 8 studies (the ninth study was funded at end of initial funding period), the central institutional review board approved the initial protocol in a mean (SD) of 59 (21) days, and additional sites were added a mean (SD) of 22 (18) days after submission. The median time from central institutional review board approval to first site activation was 47.5 days (mean, 102.1; range, 1-282) and from first site activation to first participant consent was 27 days (mean, 37.5; range, 0-96). The median time for database readiness was 3.5 months (mean, 4.0; range, 0-8) from funding receipt. In the 4 completed studies, enrollment met or exceeded expectations with 96% overall data accuracy across all sites. Nine peer-reviewed manuscripts were published, and 22 oral presentations or posters and 9 invited presentations were given at regional, national, and international meetings., Conclusions and Relevance: NeuroNEXT initiated 8 studies, successfully enrolled participants at or ahead of schedule, collected high-quality data, published primary results in high-impact journals, and provided mentorship, expert statistical, and trial management support to several new investigators. Partnerships were successfully created between government, academia, industry, foundations, and patient advocacy groups. Clinical trial consortia can efficiently and successfully address a range of important neurologic research and therapeutic questions.

Introduction: The study of histopathological changes caused by influenza A (H5N8) viral infection in bird species is essential for the understanding of their role in the spread of this highly infectious virus. However, there are few such studies under natural conditions in minor gallinaceous species. This article describes the pathomorphological findings in Colchis pheasants infected naturally with H5N8 during an epizootic outbreak in Bulgaria., Material and Methods: Samples of internal organs of 10 carcasses were collected for histopathological and immunohistochemical evaluation, virus isolation and identification, and nucleic acid detection., Results: Consistent macroscopic findings were lesions affecting the intestine, heart, lung, and pancreas. Congestion and mononuclear infiltrate were common findings in the small intestine, as were necrosis and lymphoid clusters in the lamina propria of the caeca. Congestion with small focal necrosis and gliosis with multifocal nonpurulent encephalitis were observed in the brain. Myocardial interstitial oedema and degenerative necrobiotic processes were also detected. Immunohistological analysis confirmed systemic infection and revealed influenza virus nucleoprotein in all analysed organs., Conclusion: Variable necrosis was observed in the brain, liver, trachea, heart, small intestine, and caeca. Viral antigen was commonly found in the brain, heart, lung and trachea. Contact with migrating waterfowls was suspected as a reason for the outbreak., Competing Interests: Conflict of Interest Conflict of Interests Statement: The authors declare that there is no conflict of interests regarding the publication of this article., (© 2019 G.M. Stoimenov et al. published by Sciendo.)

At the crossroad between Europe, Asia, and Africa, Bulgaria is part of the Mediterranean - Black Sea Flyway (MBSF) used by millions of migratory birds. In this study, bird species migrating through Bulgaria were investigated as carriers of zoonotic pathogens. In total, 706 birds belonging to 46 species were checked for the presence of various bacterial pathogens (Campylobacter, Yersinia, Salmonella, Listeria, Escherichia coli, Staphylococcus aureus, Francisella tularensis, Coxiella burnetii, Borrelia burgdorferi, and Brucella spp.). From 673 birds we investigated fecal samples, from the remaining 33, blood samples. We detected Campylobacter 16S rDNA gene in 1.3% of birds, but none were of pathogenic Campylobacter jejuni and Campylobacter coli species. Escherichia coli 16S rDNA gene was found in 8.8% of the birds. Out of 34 birds that transported Yersinia enterocolitica strains (5.05%), only 1 carried a pathogenic isolate. Three birds (0.4%) were carriers of nonpathogenic Salmonella strains. Four avian samples (0.6%) were positive for Listeria monocytogenes and 1 (0.15%) was positive for Brucella spp. None of the birds tested carried the tick-borne pathogens C. burnetii or B. burgdorferi sensu lato. Antibiotic-resistant strains were detected, suggesting that migratory birds could be reservoirs and spreaders of bacterial pathogens as well as antibiotic resistance genes.

Background: Most of the current scores and outcome prediction calculations in traumatology are based on the Abbreviated Injury Scale (AIS). However, this is not routinely used for documentation and coding of injuries in many countries, including Germany. Instead of the AIS, the International Classification of Diseases (ICD) is used. While the ICD functions as the basis for automated calculating of the diagnosis-related groups (DRG), no possibility of simple conversion of the 10th version of the ICD into AIS is available so far., Objectives: The aim of this work is to develop and apply a methodology for simple conversion from ICD 10 to current AIS., Materials and Methods: The developed mapping procedure was based on a 1 : n relationship between trauma codes of ICD-10-GM and the codes of the AIS2005. Calculated ISS from the conversion codes were then compared with the actual ISS coding available from the clinical trauma documentation., Results: It can be shown that, despite the considerable differences in the structure and systematic of both classification systems, an automated translation is technically possible., Conclusions: The preliminary result of the mapping suggests, however, that despite the technical feasibility of a reliable conversion and comparability of ICD 10 and AIS in the required quality is still questionable. An automated conversion is still possible and quality would possibly improve by inclusion of additional information., (Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: Responsive cortical electrical stimulation with implanted devices is under investigation for seizures. While designed to terminate seizures, might this stimulation also affect the underlying epileptic process of seizure generation?, Materials and Methods: Four patients undergoing intracranial electroencephalogram (EEG) for seizure localization had an external responsive neurostimulator (eRNS) connected to their seizure-onset zones. The eRNS detected interictal EEG spikes and stimulated at the focus. We quantified spikes at three locations: (1) near stimulation, (2) remote but in the same lobe as stimulation, and (3) in different lobe from stimulation. Ten-minute windows were analyzed at three times: (1) baseline, (2) after the first four hours of stimulation, and (3) poststimulation. One blinded investigator performed manual spike counts. Quantitative measures were total spikes, spike-free intervals (continuous ten-sec segments with no spikes), and spike clusters (one-sec intervals with three or more spikes)., Results: Some changes in spikes occurred in each patient, but no uniform pattern emerged. Two general observations were made: (1) spike counts within a given patient exhibited internally consistent changes with stimulation; (2) across patients, the nature of spike count changes varied, indicating patient-to-patient variability. For example, poststimulation, two patients had more and two patients had fewer total spikes. However, when spikes decreased near stimulation, they decreased at other sites, and when spikes increased near stimulation, they increased at other sites., Conclusions: Changes in spike occurrence, organization, and topography with stimulation suggest the eRNS affected spike generation and may affect the underlying interictal epileptic process. Case-to-case variability may be due to individual patient factors, and its significance is yet to be determined., (© 2013 International Neuromodulation Society.)

Objectives.  This study aims to assess tolerability and efficacy of stimulation parameters after vagus nerve stimulator (VNS) pulse generator replacement. Materials and Methods.  We carried out an observational, retrospective study, reviewing our experience with VNS generator replacements in 28 epilepsy patients. Results.  Seven patients had actual end of battery life (EOBL) (with symptoms), and 21 patients had asymptomatic projected EOBL. When we reprogrammed stimulation parameters postoperatively, 17 of the 28 patients could not tolerate the preoperative baseline current settings, even one year later. There were no differences in pre- vs. postoperative seizure rates between patients who did or did not return to baseline settings. Failure to return to baseline current was not related to previous VNS duration, same- vs. different-battery generator replacements, or antiepileptic medication changes. Conclusions.  After VNS generator replacement, patients' common inability to tolerate preoperative current settings does not lead to more seizures. A chronic modification of the vagus nerve system's sensitivity to stimulation changes may be hypothesized., (© 2008 International Neuromodulation Society.)

Seizure severity is an important aspect of epilepsy. The relationship between seizure severity and quality of life in epilepsy, however, has been incompletely explored. With a data set of 118 women from the baseline phase of a clinical treatment trial, the relationship between seizure severity and aspects of quality of life was evaluated. Two domains of the Quality of Life in Epilepsy-31 (QOLIE-31) correlated highly significantly with seizure severity: Seizure Worry (r=-0.265, P=.004) and Social Functioning (r=-0.280, P=0.002). Two additional domains were significantly correlated: Overall Quality of Life (r=-0.210, P=0.023) and Cognitive (r=-0.209, P=0.024). When the potentially confounding effect of depression, measured by the Beck Depression Inventory, was controlled for, the regression of seizure severity with QOLIE-31 Seizure Worry remained significant (P=0.006, R(2)=0.153), as did the regression with QOLIE-31 Social Functioning (P=0.002, R(2)=0.184) and the regression with QOLIE-31 Cognitive (P=0.037, R(2)=0.30). These findings indicate that severe and potentially injurious seizure behaviors contribute to anxiety and socially avoidant behavior for persons with intractable epilepsy.

Mortality from prostate cancer is associated with progression of tumors to androgen-independent growth and metastasis. Eicosanoid products of both the cyclooxygenase (COX) and lipoxygenase (LOX) pathways are important mediators of the proliferation of prostate cancer cells in culture and regulate tumor vascularization and metastasis in animal models. Pharmacologic agents that block either COX or LOX products effectively reduce the size of prostate cancer xenografts. Phospholipase A(2) (PLA(2)) enzymes regulate the provision of arachidonic acid to both COX- and LOX-derived eicosanoids, and a secreted form of the enzyme (sPLA(2)-IIA) is elevated in prostate cancer tissues. Here, we show by immunohistochemistry, in patients receiving androgen ablation therapy, that sPLA(2)-IIA remains elevated in remaining cancer cells relative to benign glands after treatment. Furthermore, sPLA(2)-IIA expression seen in benign glands is substantially decreased after androgen depletion, whereas cytosolic PLA(2)-alpha (cPLA(2)-alpha) levels are unchanged. sPLA(2)-IIA mRNA expression is detectable and inducible by androgen (0.01-10 nmol/L) in the androgen-sensitive cell line LNCaP, and exogenous addition of sPLA(2)-IIA (1-100 nmol/L), but not an inactive sPLA(2)-IIA mutant (H(48)Q), results in a dose-dependent increase in cell numbers or the fraction of cells in G(2)-M phase, which is inhibited by sPLA(2)-IIA-selective inhibitors. The effect of exogenous sPLA(2)-IIA can also be blocked by inhibition of cPLA(2)-alpha, suggesting a role for cPLA(2)-alpha in mediating sPLA(2)-IIAlpha action. sPLA(2)-IIA inhibitors suppressed basal proliferation in LNCaP cells and in the androgen-independent, sPLA(2)-positive cell line PC3 but not in the sPLA(2)-IIA-negative androgen-independent cell line DU145. Established PC3 xenograft tumors grew more slowly in mice treated with sPLA(2)-IIA inhibitors than those treated with saline only. The PLA(2) enzymes, and sPLA(2)-IIA in particular, thus represent important targets for the treatment of sPLA(2)-IIA-positive androgen-independent prostate cancer.

Purpose: The purpose of this study was to determine the characteristics of epilepsy that produce avoidant behavior in the workplace and therefore contribute to the actual stigma that persons with epilepsy are subjected to on the job., Methods: We developed a survey consisting three vignettes briefly describing a coworker with either depression, multiple sclerosis, or epilepsy. Each vignette was followed by eight identical questions addressing the level of comfort during interactions with the vignette subject. The epilepsy vignette did not describe a seizure. The surveys were hand-distributed in two companies in New York City and returned anonymously by mail. The results of the responses to each illness were compared by chi2, and the responses were correlated with demographic information by using Pearson's correlation., Results: Seventy-four of 200 distributed questionnaires were returned. Respondents reported more anxiety at the thought of interacting with a coworker with epilepsy than with depression or multiple sclerosis, but this difference did not reach significance. Worry about sudden, unpredictable behavior for the coworker with epilepsy was significantly greater than that with multiple sclerosis (p = 0.014). The level of comfort regarding providing first aid for the coworker with epilepsy was significantly less (p = 0.018) than that for depression and multiple sclerosis. Lower job level and lower income level correlated with more social discomfort for all three illnesses., Conclusions: The idea of a having a coworker with epilepsy may produce some social avoidance. However, the worry about a sudden, unpredictable event and the discomfort regarding providing first aid for a coworker with epilepsy is significant when compared with that with depression or multiple sclerosis. These findings suggest that education about first aid for epilepsy will reduce the worry and discomfort surrounding persons with epilepsy in the workplace., (Copyright 2004 International League Against Epilepsy)

Objective: To carry out a detailed quantitative analysis of male germ cell apoptosis in seminiferous epithelium in a long period after EDS administration., Methods: The apoptosis in adult rat testes was induced by a single i.p. injection of ethane dimethanesulphonate (EDS) in a dose of 75 mg/kg body weight. The TUNEL assay for in situ detection of apoptosis and quantitation of apoptotic germ were performed in testicular sections days 1, 3, 7, 14, 21 and 35 after EDS treatment. Plasma levels of testosterone (T) and luteinizing hormone (LH) were measured by RIA., Results: First signs of seminiferous epithelium regression were manifested by a marked increase in the number of apoptotic cells on 3rd day after EDS treatment. The maximal value of germ cell apoptosis was established on 7th day post EDS that coincided with lowest T levels. Later, until the end of investigated period, the elevated values of all investigated parameters for quantification of germ cell apoptosis decreased, but remained still higher as compared to control and, in addition, also T concentrations returned to normal range and their mean values were lower than these in controls. The pachytene spermatocytes and spermatids were the predominant cell types that underwent apoptosis after EDS treatment., Conclusions: Quantitative patterns of germ cell death after testosterone deprivation reveal in advance the kinetic of germ cell depletion and regeneration in a long period after EDS. These new findings bring additional support to the concept that germ cell apoptosis is a hormonally regulated process. Induction of germ cell apoptosis by EDS could be considered as a result of differential alterations occurring in the main testicular cell types, more than one pathway being probably involved in that physiological cell death in the testis.

Objective: To clarify the in vitro effects of inhibin A (I) on apoptotic cell death and its mechanisms in ovarian granulosa cells the immunoexpression patterns of the apoptosis markers caspase-3 and pro- and anti-apoptotic proteins (Bcl-2, Bcl-xl, Bak) were evaluated in ovarian granulosa cells collected from women with different hormonal status., Materials and Methods: Granulosa cells were isolated from follicles of women participating in an in vitro fertilization (IVF) program, normally cyclic (NC) and premenopausal women (PrM). The obtained cells were cultured for 72 h with inhibin A (Sigma, USA)--10 ng/ml. The concentration of estradiol in the culture medium was determined by radioimmunoassay using the Coat-A-Count kit (Nippon, Japan), whose intra- and interassay coefficients of variations were 6,8% and 6,2% respectively. The expression of caspase-3, Bak, Bcl-2, Bcl-xl was investigated immunohistochemically. The percentages of immunopositive cells were calculated and Student's t-test was used for statistical analysis., Results: Addition of inhibin A (10 ng/ml) to granulosa cells cultures resulted in increased estradiol production. Maximal stimulation was observed in granulosa cells collected from women participating in IVF whereas minimal effect of inhibin treatment on estradiol production was demonstrated in premenopausal women. Inhibin A exposition enhanced the immunoexpression of prooncogenes (Bcl-2, Bcl-xl) and reduced the expression of caspase-3 and pro-apoptotic protein Bak in ovarian granulosa cells from the three experimental groups., Conclusions: Our findings suggest that inhibin A in vitro stimulates the estradiol secretion by granulosa cells dependently of the woman hormonal status, while it inhibits apoptotic process in granulosa cells independently of the hormonal status.

Introduction: During the period 1996-2000, we investigated 900 couples with infertility. In 71 (7.9%) couples no cause of sterility was revealed. These patients were divided according to age, parity and infertility duration., Material and Methods: We established the cumulative conception rate and cycle fecundity after three months without therapy, after three cycles of intrauterine insemination and after three cycles of in vitro fertilization (eventually intracytoplasmic sperm injection). Among patients with less than three years of infertility, cumulative conception rate was 34.8% after three months without therapy, 27.3% after three cycles of intrauterine insemination and 66.7% after three cycles of in vitro fertilization., Results and Discussion: In patients with infertility longer than three years, cumulative conception rate without therapy was 12.5%, with intrauterine insemination 16.1% and with in vitro fertilization 40.5%. Differences regarding the age of patients were significant. Based on these findings, we proposed an optimal therapy regimen: three months therapy delay is desirable in patients under 30 years of age with infertility duration under three years. If there is no pregnancy in that period, intrauterine insemination is performed in three to four cycles. In case of intrauterine insemination failure in these women, in vitro fertilization and embryo transfer should be applied. In the group of women over 30 years of age, with infertility longer than three years, the possibility for occurrence of pregnancy with intrauterine insemination is slightly increased. If more than 4 follicles develop during preparations for intrauterine insemination, it is advisable to change the course to in vitro fertilization. In women older than 35, with primary or secondary infertility, in vitro fertilization should be performed from the very beginning.

Objective: Nitric oxide (NO) is involved in different cell functions including ovarian steroid production. Endothelin-1 (ET-1) was found to regulate the steroidogenesis in ovarian granulosa cells (GC). The present study was designed to receive more information about the mechanism of action of NO in the process of ET-1 induced progesterone (P) inhibition, using nicotine amide dinucleotide phosphate-diaphorase (NADPH-d) histochemistry as a cofactor of oxidoreductase enzymes (e. g. nitric oxide)., Methods: Granulosa cells were isolated from ovaries of: 1. young women with natural cycle or after in vitro fertilization (IVF), 2. premenopausal women. The obtained cells were cultured with endothelin-1 and the concentration of progesterone in conditioned media was determined by RIA. For the estimation of NADPH-d the histochemical reaction was used., Results: The suppressive effect of ET-1 on P production in granulosa cells was more pronounced in young women with natural cycles, slightly weaker after IVF and the most ineffective in premenopausal patients. The number of NADPH-d positive GCs was higher in young non-hormonally stimulated women, slightly lower after IVF and small in premenopausal ones., Conclusions: The results indicate the possible role of NADPH-d or NOS in the mechanism of ET-1 provoked P suppression.

EDS alkylating agent has been shown to selectively and temporarily kill LCs in adult rats. The first newly formed single LCs appeared at 14th day post ESD and showed detectable activity for 3beta-HSD and NADH2-diaphorase, which became progressively stronger with time after treatment The ultrastructural study revealed that the progenitor LCs differentiated into immature LCs within a week, and two weeks later they were transformed into mature LCs. Therefore, the restoration of new LC population after EDS treatment repeated the dynamics of normal LC development within a similar time range. The dynamics of enzyme activity correlated with structural differentiation of the new LC population.

Objective: To investigate degeneration and restoration patterns of spermatogenesis in relation to the changes in Leydig cells (LCs) after treatment with ethane dimethanesulfonate (EDS)., Materials and Methods: Adult Wistar male rats were treated with EDS at a dose 75 mg/kg body weight and the testes were sampled at 7, 14, 21, 35 and 49 days after treatment for histological and ultrastructural studies., Results: During the first two weeks after treatment stage dependent loss of germ cells was found within seminiferous tubules that led to a profound disturbance of spermatogenesis. The restoration of seminiferous epithelium followed also in stage specific manner and in relation to development of a new LC population (third week). The development of new LCs after EDS treatment repeats the normal dynamics of postnatal LC development within a similar time range., Conclusion: EDS treatment of rats causes a temporary germ cell degeneration in the testis. The kinetics of disappearance of germ cells and their regeneration broadly follows the changes in LC population.

Cell type of mammalian testis which is involved in the synthesis and secretion of testosterone and the maintenance of spermatogenesis are the fully differentiated interstitial Leydig cells (LC). Their ultrastructure possesses the typical characteristics of steroid-producing cells. It has been generally accepted that two waves of proliferation and differentiation can be discerned during the development of the Leydig cell population in the rodent and human testis. Treatment with ethane dimethane sulphonate (EDS) destroys selectively LC. A new LC population develops in the following weeks and this model has been used by us to study the proliferation and differentiation of new LC. Our results support the suggestion that the regeneration of a new LC population following EDS administration shows many similarities with the formation of the adult type LC in the prepubertal mammalian testis.

Objective: To investigate the in vitro effect of endothelin-1 (ET-1) on the steroid production (progesterone [P] and estradiol [E2]) by cultured human granulosa cells (GCs) during aging., Material and Methods: Human ovarian GCs and granulosa-luteal cells (GLCs) were isolated from ovaries of female patients (young and premenopausal) undergoing surgery for non-ovarian benign gynecological conditions. Cells were cultured with ET-1 in the presence or in the absence of FSH. The concentrations of P and E2 in conditioned media were determined by means of RIA., Results: In human GCs and GLCs obtained from young and premenopausal women, ET-1 in vitro can significantly reduce the FSH stimulated biosynthesis of P, whereas the basal P biosynthesis is only insignificantly diminished. The in vitro application of ET-1 have only a sparse inhibitory effect on both the basal and FSH stimulated biosynthesis of E2 in GCs from the two patient groups., Conclusions: Our findings support the opinion that ET-1 is a local regulator of ovarian steroidogenesis which might modulate the steroid production and the stimulatory effect of FSH in cultured GCs and GLCs obtained from women at various ages.

Context. Antiepileptic drugs (AEDs) are frequently used for their beneficial mood effects.Objective. We sought to determine if there was a quantifiable effect on mood of the vagus nerve stimulator (VNS) when used as an antiseizure treatment.Design. Mood was assessed before and 3 months after VNS implantation in adult epilepsy patients. A group of adult epilepsy patients on stable AED regimens were used as a comparison group. AED regimens were unchanged during the study. The change in mood scale scores across time was assessed by t test (intragroup) and two-factor repeated-measures ANOVA (intergroup).Setting. An epilepsy center in a university hospital was the setting.Subjects. Twenty consecutive adult epilepsy patients undergoing VNS implantation to improve seizure control and twenty adult seizure patients with no intervention were enrolled.Main outcome measures. The mood scales used were the Cornell Dysthymia Rating Scale (CDRS) and the Hamilton Depression (Ham-D), Hamilton Rating Scale for Anxiety (Ham-A), and Beck Depression Inventory (BDI) scales.Results. The VNS group showed a significant decrease in mood scale scores across time (t test CDRS P = 0.001, Ham-D P = 0.017, BDI P = 0.045), indicating a decrease in depressive symptoms. The Ham-A scores in the VNS group and the comparison group scores did not significantly change across time. There were no significant differences between groups across time, although the BDI approached significance at P = 0.07. The VNS group had a significant decrease in seizure frequency compared with the comparison group (P = 0.01). There was no difference in mood scales over time between the VNS treatment responders (defined by >50% decrease in seizure frequency) and nonresponders, suggesting dissociation between seizure frequency reduction and mood change.Conclusion. VNS treatment is associated with mood improvement as measured by multiple scales, but differences in mood scale scores over time between the VNS and a comparison group were not found.

Objective: To localize (by the light and electron microscopy) and partially characterize the antigen recognized by the Mab4E6 in rat ovaries., Methods: Monoclonal antibody (4E6) against a rat ovarian granulosa cell antigen was prepared and identified the 40kDa protein specific for rat steroid producing cells. The localization of this antigen was studied by light and electron microscopic immunocytochemistry., Results: The immunocytochemical observation suggested that the recognized antigen was localized in granulosa and thecal cells in all stages of follicular development. The intensity of immunostaining was found to depend on the developmental stage. In granulosa and thecal stage (health follicle) Mab 4E6 binding molecule was localized on the membranes of rough endoplasmic reticulum (RER) and on the surface of lipid droplets in close association with the RER. In atretic follicles we established that the final destination of the visualized antigen is in structures which we refer as the autophagic vacuoles in close contact with the steroidogenic organelles. In addition, we observed Mab 4E6 binding molecule in the cytoplasm of luteal cells. Leydig cells and adrenocortical cells., Conclusions: The results indicate that the 40kDa antigen may be common to all of rat steroidogenic organs. Our results suggest that the 40kDa protein may be associated with the processes governing steroidogenesis and/or follicular development.

Purpose: Antiepileptic drugs (AEDs) are frequently used for their beneficial psychoactive effects on affective disorders. We sought to demonstrate a psychoactive effect of gabapentin (GBP) when used as add-on AED therapy., Methods: Forty adult patients with partial epilepsy were studied in a prospective, non-randomized fashion with interviewer-rated and self-rated scales of mood and anxiety: the Cornell Dysthymia Rating Scale (CDRS), Beck Depression Inventory (BDI), and Hamilton Depression (Ham-D) and Anxiety (Ham-A) Scales. After completion of baseline mood and anxiety scales (time 1), 20 of the 40 patients were prescribed add-on GBP (treated group). The remaining 20 patients served as a control group. Both groups were similar in age and sex distribution. Follow-up mood and anxiety scales were performed in all patients approximately 3 months later (time 2). The average GBP dose at time 2 was 1,615 mg/day. All patients were taking stable doses of one to four AEDs at baseline and throughout the study. Seizure frequency was monitored throughout. Statistical significance was assessed by analysis of variance (ANOVA) by using a two-factor repeated-measures model., Results: The GBP-treated group had a significant decrease in CDRS score over time compared with the control group (p = 0.04). No significant differences between the control and the treated groups were found for any of the remaining mood scales (BDI, p = 0.58; Ham-D, p = 0.59; Ham-A, p = 0.93). There was no significant difference or change in seizure frequency between groups., Conclusions: GBP treatment is associated with mood improvement as measured by the CDRS. This improvement was not accounted for by seizure improvement.

Objective: To extend our previous observations of granulosa cell conditioned medium inhibition on basal and FSH-stimulated progesterone secretion by granulosa cells from large porcine antral follicles., Methods: Granulosa cell conditioned media (SGCCM) were obtained from cultures of granulosa cells which were harvested from small porcine antral follicles. SGCCM were fractionated by filtration through an Amicon XM-50 and an PM-10 membrane., Results: Two fractions - XM-50 filtrate (<50 kDa) and PM-10 retentate (10-50 kDa) - exhibited well expressed inhibitory effect on the progesterone secretion from large follicle granulosa cells in vitro. Such inhibitory effect was fully prevented by heat treatment, partially inactivated by trypsin digestion (P<0.05), but was resistant to several freeze-thaw cycles and storage at -20 or -70 degrees C for up to one year., Conclusions: It is suggested that SGCCM contains some regulatory substance(s) capable of inhibiting progesterone secretion by cultured granulosa cells and that the molecular weight of such substance is presumably between 10-50 kDa.

Purpose: Patients with symptomatic generalized epilepsy (SGE) may have antiepileptic drug (AED)-resistant mixed generalized seizures. Vagus nerve stimulation (VNS) reduces partial seizures and may help SGE., Methods: We added VNS to stable AED therapy in five SGE patients. Nine-month postoperative VNS treatment seizure rates were compared to a 1-month preoperative baseline., Results: All patients had mixed generalized seizures, EEG generalized slow spike-and-wave and behavioral abnormalities. Median number of previous AEDs taken was 6 (range 5-12). Median baseline seizure rate was 75/month (range 29-110). VNS produced a median seizure rate production of -41% (range -40% - -85%). Adverse events reported in one patient each were: incisional infection, choking sensation and voice change; and coughing (noted by two patients). One patient discontinued VNS due to coughing., Conclusions: We conclude that VNS may be useful add-on therapy for SGE. A larger, controlled, and blinded trial may be warranted.

Morphometrical and cytochemical techniques have been applied to characterize the islets of Langerhans tissue in lean and obese Zucker fa/fa and Wistar rats. The changes in cytologic composition correlated with levels of serum glucose and lipids in obese rats and progressed significantly with increasing body weight. Histochemical and enzyme abnormalities observed in Zucker fa/fa and Wistar rats reflect the degenerative and reactive processes in the pancreas: a decrease in Krebs cycle and pentose pathway and increased lysosomal acid phosphatase reflect the degeneration of the islets. Changes consisted of pronounced insulin cell hyperplasia and disruption of islet architecture. The raised functional activity in the islet B-cells of the Zucker fa/fa and Wistar rats was reflected in enlargement and fragmentation of the Golgi apparatus. An increased proportion of light granules is associated with increased insulin secretion, which reinforces the idea that light granules are responsible for immediate insulin secretion, whereas the dark granules represent the insulin stored in the cell for a longer period The islets of Langerhans of the Zucker fa/fa and Wistar rats show marked differences in morphological, histochemical and morphometrical characteristics when compared with littermates. There is a marked difference in insulin secretion between the obese Zucker fa/fa and Wistar rats and its non-obese littermate. These differences may be related to the development with obesity of aging and genetically-conditioned animals.