Does miliary sarcoidosis really exist? A case report and review of the literature.

BACKGROUND: Miliary sarcoidosis is a rare form of sarcoidosis characterized by numerous miliary-like micronodules dispersed throughout the lungs. It has been documented in less than 1% of all sarcoidosis cases. We first described a rare case of miliary sarcoidosis and then conducted a literature review on the subject. CASE PRESENTATION: A 51-year-old male complained about a progressive loss of appetite, significant weight loss, occasional night sweats, and fatigue. After a thorough clinical exploration, a differential diagnosis of miliary lung disease was suspected - miliary tuberculosis, fungal infection, metastatic pulmonary carcinoma, or sarcoidosis. High-resolution chest computed tomography revealed bilateral diffuse micronodules with mediastinal lymphadenopathy. Histopathological analysis of transbronchial bioptic tissue identified non-caseating epithelioid granulomas, while no malignant cells were found. Lung tuberculosis and fungal infections were excluded. The levels of angiotensin-converting enzyme in the blood, as well as serum's and 24-hour urine calcium levels, were elevated. After a multidisciplinary discussion, the diagnosis of miliary pulmonary sarcoidosis was established. The patient was treated with prednisone for a total of 9 months, with full clinical and radiological recovery. Using PubMed, we also conducted a review of the literature on this topic and discovered only a few case reports of patients with miliary sarcoidosis, with just one systematic review accessible. The key findings of studies investigating patients diagnosed with miliary sarcoidosis are tabularly displayed. CONCLUSIONS: Miliary sarcoidosis is an uncommon type of pulmonary sarcoidosis that can mimic several entities that manifest as miliary nodules. Most patients require treatment since it can have a significant impact on lung function.

The COVID-19 pandemic - related psychological distress and job burnout among Serbian pharmacy practitioners: a cross-sectional online study.

OBJECTIVE: The current COVID-19 pandemic has increased occupational stress for all healthcare providers, making job burnout one of the most common and largely unrecognized mental health issues among healthcare professionals. Besides physicians and nurses, pharmacy practitioners were "front-line" healthcare professionals with a critical and unique role in the public health crisis. Considering this, the aim of this study was to examine distress levels and the prevalence of job burnout among Serbian pharmacy practitioners in relation to the COVID-19 pandemic. SUBJECTS AND METHODS: This cross-sectional online study was conducted in April and May of 2020. A total of 176 pharmacy practitioners anonymously and voluntarily completed the two-section questionnaire, consisting of Copenhagen burnout inventory, CBI and 4DSQ Distress subscale. The two-section questionnaire was distributed online, among various social-media groups of pharmacy practitioners, as well as by personal contacts following the "snowball" sampling method. RESULTS: Results revealed moderately high burnout scores in our sample. The majority of the participants showed signs of personal-related job burnout, followed by work-related and client-related burnout. A strongly elevated distress level was obtained in almost two-thirds of study respondents. In addition, a significant and high correlation of all CBI subscales with distress was found, as well as medium correlations with sleep duration shortening as a mediator between distress and job burnout. CONCLUSIONS: Results of our study showed that job burnout significantly increased among pharmacy practitioners during the COVID-19 pandemic. Furthermore, we discovered that stress has an indirect impact on study participants' burnout via insufficient sleep.

Measuring pharmacovigilance knowledge and attitudes among healthcare sciences students: development and validation of a universal questionnaire.

OBJECTIVE: Pharmacovigilance education and reporting of adverse drug reactions (ADRs) are important competencies that healthcare sciences students should develop before completing their studies and entering clinical practice. Since students frequently lack adequate knowledge in this area and fail to recognize the importance of ADRs monitoring and reporting, the aim of this study was to develop and validate a unique and reliable instrument for assessing health sciences students' knowledge and attitudes toward pharmacovigilance and ADRs reporting. SUBJECTS AND METHODS: A cross-sectional observational study was conducted from February to July 2021 to examine students' knowledge and attitudes toward pharmacovigilance activities. Students of medicine, dentistry, pharmacy, and nursing science of three faculties in the Autonomous Province of Vojvodina, Serbia were examined. A total of 211 of them completed the specially designed, three-section questionnaire (Demographic data section, Pharmacovigilance Knowledge test, PVKT, and Pharmacovigilance Attitude Questionnaire, PVAQ). The questionnaire was posted on the Google Forms platform, and the link was distributed to respondents via the official websites and social networks of all three faculties. RESULTS: Findings demonstrated good psychometric properties and reliability of the questionnaire. Six questions were removed from the PVKT after item analyses. After excluding these items, the calculated ordinal alpha of the final version of the PVKT, which included 14 items, was good (αord = 0.83), as were other statistical indicators. PVAQ reliability testing also revealed great performance of this questionnaire-calculated ordinal alpha for two PVAQ subscales was excellent (αord = 0.91, for both scales). CONCLUSIONS: This questionnaire has favorable validity and reliability in assessing healthcare sciences students' knowledge and attitudes toward pharmacovigilance and ADRs reporting.

COVID-19 associated pulmonary embolism with D-dimer values within the referent range: a case report and review of the literature.

OBJECTIVE: COVID-19 is associated with an increased incidence of pulmonary embolism (PE). Elevated D-dimer levels are linked to an increased risk of PE and poor clinical outcome. We reported a case of PE in a COVID-19 patient with normal D-dimer levels and conducted a review of the literature on the subject. CASE REPORT: A 38-year-old man with no prior comorbidities returned to the COVID-19 outpatient clinic 36 hours after being discharged from the hospital, where he had been treated for COVID-19 pneumonia. He reported a sudden feeling of dyspnea and chest pain. The physical examination was unremarkable. No new changes were detected on the chest X-ray. D-dimer and cardiac-specific markers values were within the referent range. The patient underwent an urgent computerized tomography pulmonary angiography which revealed signs of bilateral arterial thrombosis. He was treated with a therapeutic dose of low molecular weight heparin and discharged after 15 days, with a recommendation to use a direct oral anticoagulant. CONCLUSIONS: Healthcare professionals should be aware that PE can occur as a late complication of COVID-19. Clinical suspicion of PE should lead physicians to use additional diagnostic methods to confirm or rule out PE, even if D-dimer levels are within the referent range.

Human leukocyte antigen class II (DRB1 and DQB1) alleles and haplotypes frequencies in patients with pemphigus vulgaris among the Serbian population.

The etiology of pemphigus vulgaris (PV) is multifactorial and includes genetic, environmental, hormonal, and immunological factors. Inheritance of certain Human class II leukocyte antigen (HLA) alleles is by far the best-established predisposing factor for the development of PV. Class II HLA alleles vary among racial/ethnic backgrounds. We have determined an association between HLA class II alleles and PV among the Serbian population. A total of 72 patients with confirmed diagnosis of PV were genotyped for HLA class II alleles. HLA frequencies were compared with unrelated healthy bone marrow donors. The statistical significance of differences between patients and controls was evaluated using Fisher's exact test. The DRB1*04 and DRB1*14 allelic groups were associated with PV (P adj = 4.45 × 10(-13) and 4.06 × 10(-19) respectively), while HLA-DRB1*11 was negatively associated with PV (P adj = 0.0067) suggesting a protective role. DRB1*04:02, DRB1*14:04, DQB1*03:02 and DQB1*05:03 alleles were shown to be strongly associated with PV (P adj = 1.63 × 10(-12), 5.20 × 10(-7), 1.28 × 10(-6), and 4.44 × 10(-5), respectively). The frequency of HLA DRB1*04-DQB1*03 and HLA DRB1*14-DQB1*05 haplotypes in PV patients was significantly higher than in controls (31.3% vs 8.8%, P adj =7.66 × 10(-8) and 30.6% vs 6.3%, P adj = 3.22 × 10(-10), respectively). At high-resolution level, statistical significance was observed in HLA-DRB1*04:02-DQB1*03:02 and HLA-DRB1*14:04-DQB1*05:03 haplotypes (P adj = 5.55 × 10(-12), and P adj = 3.91 × 10(-6), respectively). Our findings suggest that HLA-DRB1*04:02, DRB1*14:04, HLA-DQB1* 03:02 and DQB1*05:03 alleles and HLA-DRB1*04:02-DQB1*03:02 and HLA-DRB1*14:04-DQB1*05:03 haplotypes are genetic markers for susceptibility for PV, while DRB1*11 allelic group appears protective in Serbian population.

A rare case of aneurymal bone cyst of cuboid bone in a 10-year-old girl.

Aneurysmal bone cysts (ABC) are rare and they represent 1- 1.4 % of all primary bone tumors. ABC of cuboid bone are extremely rare, especially in children. Very few cases have been reported in the literature since 1967. We present a case of pathological fracture of cuboid bone due to an aneurysmal cyst in a 10-year-old girl. Surgery was performed, which included open biopsy with aspiration and intralesional curettage . Bone defect was then filled in by fully synthetic cancellous bone graft substitute consisting of pure ß-tricalcium phosphate. Aneurysmal cyst of cuboid bone with pathological fracture could be successfully treated with pure ß-tricalcium phosphate as a bone graft substitute. This procedure is safe with excellent outcome.Follow up to nearly four years did not show any recurrence.

Bilateral Septic Neonatal Orchiepididymitis - Case Report.

Neonatal epididymo-orchitis is a rare condition, causing testicular pain in neonatal boys. It represents epididymo-testicular inflammation which commonly coexists with urinary tract infections and malformations. The idiopathic type is extremely rare. We present a case of a seven-day old male neonate with advanced septic form of idiopathic orchiepididymitis and no associated urinary tract anomalies. The boy was hospitalized with signs of sepsis, anterior abdominal wall phlegmona and bilateral acute scrotum. Colour Doppler echosonography indicated epididymo-testicular inflammation with increased vascular flow. The patient underwent surgical exploration of both scrota in order to evacuate purulent content and fibrin. Cultures of Enterobacter spp were detected in hemiscrotal pus. Prompt administration of antibiotics was done. The postoperative course was uneventful. We suggest that every male baby must be very meticulously examined by a neonatologist in the early postnatal period, in order to prevent infertility.

Blunt Trauma in Paediatric Patients - Experience from a Small Centre.

OBJECTIVE: Despite great prevention efforts, blunt abdominal trauma still remains a leading cause of injury, especially in the paediatric population. Abdominal trauma is the main culprit of serious children's injury and the most common area of initially missed diagnosis with a fatal outcome. AIM: The purpose of this study was to determine the incidence, aetiology, grades of abdominal organ injuries, diagnosis, management and outcome of blunt abdominal trauma in a paediatric population. METHOD: This is a retrospective study of 31 patients with isolated parenchymatous abdominal organs, treated in a single centre. Stable patients with no signs of peritonitis and insignificant changes in laboratory findings were managed conservatively. Unstable patients received surgery. RESULTS: The leading cause of injuries were traffic accidents (64.5%), followed by fall from a height (22.5%), bicycle handlebar injuries (6.45%), contact sport and child abuse (3.22% each). The majority of injured children (90.32%) were managed conservatively. Only three patients (9.68%) were operated on due to complete avulsion and organ smash, or devascularization of the injured organs. Diagnostic computed tomography (CT) scan examination was performed on 93.5% of patients. Few patients had grade I and grade V injuries, while the largest proportion of patients had grade III and IV injuries. The most frequently injured organs were the spleen and kidney. There was no mortality. CONCLUSION: The results emphasize that conservative treatment was appropriate for all stable patients with blunt abdominal trauma regardless of organ injury grade. The success of non-operative management depends upon proper patient selection. The choice of non-operative treatment should be based predominantly on physiological response, rather than grade injury on CT scan.

Biomarkers of oxidative stress and endothelial dysfunction after tourniquet release in children.

Pneumatic tourniquets are widely used in pediatric extremity surgery to provide a bloodless field and facilitate dissection. This prospective study was carried out to examine possible effect of different anesthesia techniques on oxidative stress and endothelial dysfunction connected with ischemia-reperfusion injury during extremity operations at children's age. Patients were randomized into three groups of 15 patients each: general inhalational anesthesia with sevoflurane (group S), total intravenous anesthesia with propofol (group T) and regional anesthesia (group R). Venous blood samples for determination of the malondialdehyde in plasma and erythrocytes, protein carbonyl groups concentration as well as plasma nitrites and nitrates level and xanthine oxidase activity were obtained at four time points: before peripheral nerve block and induction of general anesthesia (baseline), 1 min before tourniquet release, 5 and 20 min after tourniquet release. This study demonstrates that total intravenous anesthesia with propofol and regional anesthesia techniques provide better antioxidant defense and reduce endothelial dysfunction than general inhalational anesthesia with sevoflurane during tourniquet application in pediatric extremity surgery.

Long-term outcome in Serbian patients with Wilson disease.

BACKGROUND AND PURPOSE: To investigate survival rates, prognostic factors, and causes of death in Wilson disease (WD). METHODS: In the years 1980-2007, a cohort of 142 patients with WD was prospectively registered (54 presented with neurologic symptoms, 49 with hepatic symptoms, 33 had mixed form, and data were missing for six patients). The duration of follow-up for patients alive was 11.1 +/- 8.8 years. RESULTS: After initiation of treatment (d-penicillamine and zinc salts), 79% of patients had a stable or improved course of disease. Despite early diagnosis and appropriate therapy, 15 patients still had a relentlessly progressive course. Thirty patients died. The cumulative probability of survival in a 15-year period for the whole group was 76.7 +/- 4.9%. Better prognosis of WD was associated with male sex, younger age at onset, neurologic form of the disease, and treatment continuity. Causes of death were predominantly related to hepatic failure (16 patients), but also suicide (four patients) and cancer (three patients). CONCLUSION: Despite the relatively early diagnosis and treatment of our patients with WD, mortality was still considerably high.

Gastroesophageal reflux in infants and children.

Gastroesophageal reflux disease (GERD) is the most common esophageal disorder and the most frequent reason why infants are referred to the pediatric gastroenterologist, affecting as much as 30% of the pediatric population. Presenting features of GERD in infants and children are quite variable and follow patterns of gastrointestinal and extra-esophageal manifestations that vary between individual patients and may change according to age. Patients may be minimally symptomatic, or may exhibit severe esophagitis, bleeding, nutritional failure, or severe respiratory problems. GERD is also complex for the diagnostic techniques required to assess its repercussions or explain its origin. Although different abnormalities in motility variables, such as lower eso-phageal sphincter (LES) function, esophageal peristalsis and gastric motor activity can contribute to the development of GERD, the degree of esophageal acid exposure represents the key factor in its pathogenesis. Esophageal pH monitoring, based on both the detection of acid reflux episodes and the measurement of their frequency and duration, has been regarded as the most sensitive and specific diagnostic tool for diagnosing reflux disease. The aim of this paper is to give a concise review for the clinicians encountering this specific disease in infants and children.

Valproate and delta-sleep peptide display high efficacy against metaphit-induced audiogenic seizure in rats.

The effects of valproate (VPA) and delta sleep-inducing peptide (DSIP) on metaphit-induced generalized, audiogenic seizure in adult rat males were compared. The animals were i.p. injected with: (1) Saline; (2) metaphit (mp, 10 mg kg(-1)); 3. metaphit (10 mg kg(-1)) and 8 h later with DSIP (0.1, 0.2, 0.4 or 1.0 mg kg(-1)), 4. metaphit (10 mg kg(-1)) and 8 h later with VPA (50, 75 or 100 mg kg(-1)); 5. DSIP alone (1.0 mg kg(-1)) and 6. VPA, alone (100 mg kg(-1)). The rats were exposed to sound stimulation at hourly intervals and the behavior and EEG were analyzed. The EEG signals in metaphit rats appeared as a sleep-like pattern and spike-wave complexes with increased power spectra. Valproate and DSIP reduced the incidence of seizure and prolonged duration of latency in a dose-dependent manner. ED50 of valproate in the 1st hour after administration was 63.19 mg kg(-1) and that of DSIP 3.19 mg kg(-1) four hours after injection. This suggests that VPA, reached a peak of action immediately after the application, while DSIP had a prolonged action, mildly reducing, but not abolishing metaphit seizure. None of the applied VPA and DSIP doses eliminated the metaphit-provoked EEG signs of epileptiform activity.

Different effects of nonNMDA and NMDA receptor antagonists (NBQX and dizocilpine) on cortical epileptic afterdischarges in rats.

Excitatory amino acids play an important role in generation of epileptic seizures. To study the participation of different types of their receptors in cortical epileptic afterdischarges, a noncompetitive NMDA receptor antagonist dizocilpine and a competitive AMPA receptor antagonist NBQX were used. Adult rats with implanted epidural stimulation and registration electrodes were pretreated either with NBQX (30 or 60 mg/kg i.p.) or with dizocilpine (0.1 or 0.5 mg/kg i.p.) and low-frequency stimulation of sensorimotor cortical area was repeatedly applied with stepwise increased current intensities. Lower dose of NBQX unexpectedly decreased thresholds for elicitation of spike-and-wave afterdischarges (ADs), clonic seizures accompanying this type of ADs and for transition into the second, limbic type of ADs. Lower dose of dizocilpine increased these three thresholds. Higher doses of either drug did not significantly change threshold intensities. Duration of ADs was also influenced by the two antagonists in opposite directions: higher dose of NBQX resulted in prolongation of ADs mainly due to an increased duration of the spike-and-wave part of ADs whereas dizocilpine shortened ADs in a dose-dependent manner affecting both types of ADs. In addition, NBQX did not influence interhemispheric responses meanwhile dizocilpine moderately suppressed these evoked potentials. According to our results, NMDA receptors are important for generation of cortical epileptic afterdischarges meanwhile the role of AMPA receptors is not clear and has to be analyzed.

[An acute pancreatitis in a child caused by Na-valproate]. / Akutni pankreatitis kod deteta uzrokovan Na-valproatom.

Na-valproat (Apilepsin, Eftil), is is a commonly prescribed medication approved for treatment of epilepsy, trigeminal neuralgy, migraine, and bipolar disorder. Although the common adverse effects associated with Na-valproat are usually benign, more serious and fatal complication like liver failure and acute pancreatitis (AP) can occur. Acute pancreatitis may take place in all ages, regardless of dose and serum levels of the medicine. An acute pancreatitis is relatively common after intravenous administration. The authors presented a case of acute opancreatitis in 13-years girl caused by Na-valproat.

Action of GABA-B antagonist on cortical epileptic afterdischarges in rats is similar to that of GABA-A antagonist.

Threshold intensities for epileptic phenomena induced by cortical stimulation were used for comparison of the action of GABA-B and GABA-A antagonists in rats with implanted electrodes. Both CGP 35348 (200 mg/kg i.p.) and bicuculline (4 mg/kg i.p.) significantly decreased thresholds for spike-and-wave afterdischarges and their motor counterpart (clonic seizures) whilst transition into the second, limbic type of afterdischarge as well as threshold for movements directly bound to stimulation remained uninfluenced by either drug.

[The delta-sleep inducing peptide and its effect on the electroencephalogram and power spectrum density in rats with metaphit-induced epilepsy]. / Delta-peptid spavanja i njegov uticaj na elektroencefalogram i spektralnu gustinu snage kod pacova s metafitskom epilepsijom.

INTRODUCTION: Sleep has many common features with epilepsy (spontaneously, recurring event and EEG hypersynchrony including EEG potentials that look very similar to epileptiform sharp waves) [1]. Monnier et al. [4] reported the presence of a sleep-inducing factor inducing sleep with predominant EEG activity in the 8 band (1-4 Hz), and it was the reason for the term delta sleep-inducing peptide (DSIP). Metaphit was synthesized by Rafferty et al. (1985) [7] and was shown to increase general brain excitability and induce audiogenic seizures in small rodents. The effects of a natural somnogenic nonapeptide DSIP on metaphit-induced audiogenic epilepsy in rats were studied with the aim of shedding more light on answering the question whether DSIP could be included in the list of antiepileptic agents. MATERIALS AND METHODS: Adult, 2-month-old male Wistar rats (170-200 g) were used. None of the animals screened for audiogenic susceptibility showed seizure activity. Audiogenic stimulation was used for 60 s using an electric bell (100 +/- 3 dB 5-8 kHz). Rats were divided into four groups: 1. Control, saline-injected (n = 6); 2. metaphit administered (10 mg/kg; n = 12); 3. metaphit + DSIP (1 mg/kg), (n = 14) group, DSIP administered after 8th to investigate blocking effect on fully developed metaphit seizure. 4.DSIP alone (1 mg/kg, n = 6). RESULTS: In control saline-injected animals AGS provoked no convulsive response. Metaphit injection produced after 30 min initial EEG changes in the form of synchronized spikes and fast high-voltage activity that are typical seizure manifestations, power spectra increased and became more intense in the period of sound onset and seizure events. Our results demonstrate that DSIP acted increasing the EEG output in the 8 range and significantly elevated the mean power spectra in all checked experimental points. Besides, DSIP decreased the incidence and duration of convulsive component, as well as mean seizure grade in metaphit-induced seizures. DISCUSSION: Metaphit induces a generalized, reflex epilepsy thus providing an experimental model of choice for the studies of the mechanism of epilepsy development and blockade of NMDA/PCP receptors. In our previous studies a competitive NMDA antagonist CPP [9] and a noncompetitive antagonist MK-801 [8] were used. Non-competitive, selective NMDA antagonists MK-801, PCP and ketamin expressed a partial agonist motor action (myoclonic jerks, ataxia and tremor of the whole body) in audiogenic epilepsy prone mice. DSIP produced no harmful effects even when overdosed or any effect over "normality" [4, 5]. DSIP has a capacity of suppressing various forms of convulsive activity in different animal species. It was suggested that it exerts an anticonvulsant action by influencing neurotransmitter (dopaminergic, adrenergic, GABA-ergic) and neuromodulator (peptidergic) brain systems [12, 13]. CONCLUSION: Our results, together with the fact that DSIP penetrates through the blood brain barrier after systemic administration and that overdoses of this natural peptide produce no harmful effects, strongly suggest that it could be an important therapeutic agent for the treatment of sleep disturbances. Also, our data demonstrating reduction in incidence, severity and duration of seizure components, suggest that this agent might be a suitable candidate as an antiepileptic drug.

N-Methyl-D-aspartic acid- and metaphit-induced audiogenic seizures in rat model of seizures.

The effects of NMDA (N-methyl-D-aspartic acid) on metaphit (1-[1(3-isothiocyanatophenyl)-cyclohexyl]piperidine)-induced audiogenic seizures in adult male Wistar albino rats were studied with the aim of developing a suitable animal model of seizures. The animals were divided into four experimental groups: 1, saline control; 2, metaphit-injected; 3, metaphit + NMDA administered and 4, NMDA-treated. Upon the treatment, the rats were exposed to sound stimulation (100 +/- 3 dB, for 60 s) at hourly intervals and the incidence and severity (running, clonus and tonus) of seizures were analysed. In group 3, only the animals which did not exhibit any metaphit-induced audiogenic seizures over 8 h were given a subconvulsive NMDA dose after the eighth audiogenic testing. For EEG recordings, three gold-plated screws were implanted into the rat skull. In most animals, metaphit led to EEG abnormalities and elicited epileptiform activity recorded as spikes, polyspikes and spike-wave complexes. Maximum incidence and severity of metaphit-induced convulsions occurred 8 h after injection (incidence 9/12), abating gradually until disappearing 30 h later. NMDA alone provoked no seizure response but the initial signs characterized by isolated spike activity evolving into sporadic slow-wave complexes, thus representing a proconvulsive brain state, were observed. This compound led to stereotyped behaviour seen as asymmetric posture, loss of righting reflex and tonic hind limb extension lasting for 60-90 min. It also potentiated metaphit-induced audiogenic seizures. Potentiation of metaphit-related audiogenic seizures by NMDA was recorded in three out of 17 rats that had never displayed seizures in eight previous testings, with a maximum incidence of eight out of 17 animals, 13-14 h after metaphit administration and seizures lasted for 10 h.

[Potentiation of metaphit-induced audiogenic epilepsy with N-methyl-D-aspartate in rats]. / Potencijacija audiogene metafitske epilepsije en-metil-de-aspartatom kod pacova.

INTRODUCTION: Audiogenic seizures (AGS) are induced by high intensity sound stimulation in genetically susceptible rats or in animals subjected to chemical or electrical manipulation. Epileptic seizure may result from an impaired balance between excitation and inhibition in the CNS. The effect of NMDA (N-methyl-D-aspartic acid) on metaphit 1-(1(3-isothiocyanatophenyl-ciclohexyl)-piperidine) induced audiogenic seizures was evaluated in rats. METHODS: Male Wistar albino rats were divided into 4 groups: 1) saline; 2) metaphit (10 mg/kg); 3) metaphit + NMDA; 4) NMDA (70 mg/kg). Animals were injected with metaphit intraperitoneally (i.p.) and exposed to sound stimulation (100 +/- 3 dB, 60 s) at hourly intervals. The incidence and severity (running, clonus and tonus) of seizures were analyzed. NMDA alone was administered i.p. to 6 rats. In group metaphit + NMDA only animals which did not exhibit any seizure during 8 hours were injected with NMDA i.p. after the 8th audiogenic testing. For electroencephalograph (EEG) recordings three gold-plated screws were used. Convulsive behaviour was assessed by incidence of motor seizure and by seizure severity grade, determined by use of a descriptive rating scale with range of 0-3; 0-no response; 1-wild running only; 2-wild running followed by clonic seizures of all four limbs with body rollover; 3-wild running progressing to generalized clonic convulsions and then a tonic extension of the fore and hind limbs and tail. Sound onset, seizure events, and sound offset, along with the animals behaviour (convulsive or other) were recorded as the correlates to the respective EEG responses. RESULTS: In most animals the administration of metaphit (10 mg/kg) resulted in electrographic abnormalities, elicited epileptiform activity in the form of spikes, polyspikes and spikewave complexes (Fig. 1.). Maximum incidence and severity of metaphit convulsions occurred 8 h after the injection (9/12, 75%) (Fig. 2, 3.), then abated gradually and disappeared 30 h later. NMDA (70 mg/kg) alone induced no seizure response but isolated spiking activity, and sporadic slow-wave complexes were recorded (Fig. 4). NMDA induced stereotyped behaviour in the form of asymmetric posture, loss of righting reflex and tonic hindlimb extension, which lasted for 60-90 min. Subconvulsive dose of NMDA potentiated the metaphit-induced audiogenic seizures in rats. Two hours after NMDA administration 3 of 17 metaphit-treated rats convulsed, which in 8 previous testings never displayed seizures. Maximum incidence was 8 of 17 (53%), 5-6 h after NMDA administration and seizures lasted for 9 hours. DISCUSSION: Several authors reported that metaphit dose of 10 mg/kg accompanied by some REM sleep deprivation (REM-D) procedures [4], or subconvulsive doses of NMDA [25] provoked seizures of higher intensity and incidence. Metaphit treatment (10 mg/kg) followed 24 h later by NMDA dose of 50 mg/kg provoked no spontaneous convulsions, while metaphit in combination with a higher NMDA dose of 70 mg/kg resulted in spontaneous and AGS-induced seizures only in one time point [25]. It was found that the incidence and severity of convulsive responses were highest 8-12 h after metaphit injection (10 mg/kg) [23, 24]. Although about 8 h after metaphit administration the power spectra increased and were more intense in the period of sound onset and seizure events. CONCLUSION: The results of the present study strongly suggest that treatment of adult rats with the combination of metaphit and NMDA in the doses employed here followed by AGS provides a suitable animal model for examinations of epileptic seizures.

The effect of delta sleep-inducing peptide on the EEG and power spectra in rat.

The effects of delta sleep-inducing peptide (DSIP) on the EEG and power spectra of adult male Wistar rats (b.w. 180-220 g) were studied by power spectra analyses of EEG wave forms recorded continuously for 12 h after DSIP administration. The animals were given DSIP i.p. (1 mg/kg). Saline-injected rats served as the corresponding control. Recorded bursts of high amplitude EEG in the 1-9 Hz range (delta and theta) were found to be more frequent in DSIP-treated animals, while power spectra and (delta) wave activity were enhanced in comparison with the control and a statistically significant increase was registered in all experimental points after DSIP (2 h P < 0.05; 4 h P < 0.05; 5 h P < 0.05; 6 h P < 0.05; 7 h P < 0.01; 11 h P < 0.05). In addition, DSIP significantly elevated both the EEG output in the (delta) range and sleep activity. These results suggest that DSIP should be considered as a potential agent for the treatment of sleep disturbances in human medicine.