Prospects of toll-like receptors in dairy cattle breeding.

Toll-like receptors (TLRs) play an important role in mediating the immune response against various microbes, such as bacteria, viruses, parasites, and fungi, in innate and adaptive immunity. Ten functional TLRs (TLR1 to TLR10) have been identified and mapped in cattle, with each TLR recognising specific pathogen-associated molecular patterns. The variation in genes controlling the immune response contributes to susceptibility or resistance to various infectious diseases such as mastitis, bovine tuberculosis, and paratuberculosis. Identifying TLR SNPs shows promising results for future marker-assisted breeding strategies, screening for disease risks, and improving the genetic resistance of dairy cattle. This article aims not only to review the research into susceptibility or resistance to infectious diseases and milk production traits in dairy cattle but also to discuss the limitations in current studies and the prospects in dairy cattle breeding.

The effect of subchronic supplementation with folic acid and l-arginine on homocysteine-induced seizures.

The aim of the present study was to examine the effect of subchronic co-administration of folic acid (F) and l-arginine (A) on behavioural and electroencephalographic (EEG) characteristics of dl homocysteine thiolactone (H) induced seizures in adult rats. The activity of membrane ATPases in different brain regions were also investigated. Rats were treated with F, A, or vehicle for 15 days (regimen: F 5 mg/kg + A 500 mg/kg (F5A500); F 10 mg/kg + A 300 mg/kg (F10A300)). Seizures were elicited by convulsive dose of H (H, F5A500H, F10A300H) Subchronic supplementation with F and A did not affect seizure incidence, number of seizure episodes, and severity in F5A500H and F10A300H groups vs. H group. However, a tendency to increase latency and decrease the number of seizure episodes was noticed in the F10A300H group. EEG mean spectral power densities during ictal periods were significantly lower in F10A300H vs. H group. The activity of Na+/K+-ATPase and Mg2+-ATPase was significantly increased in almost all examined structures in rats treated with F and A. We can conclude that subchronic supplementation with folic acid and l-arginine has an antiepileptic effect in dl homocysteine thiolactone induced epilepsy.

Homocysteine thiolactone-induced seizures in adult rats are aggravated by inhibition of inducible nitric oxide synthase.

Homocysteine and its metabolites (homocysteine thiolactone (HT)) induce seizures via different but still not well-known mechanisms. The role of nitric oxide (NO) in epileptogenesis is highly contradictory and depends on, among other factors, the source of NO production. The aim of the present study was to examine the effects of aminoguanidine, selective inhibitor of inducible NO synthase (iNOS), on HT-induced seizures. Aminoguanidine (50, 75, and 100 mg/kg, intraperitoneally (i.p.)) was injected to rats 30 min prior to inducing HT (5.5 mmol/kg, i.p.). Seizure behavior was assessed by seizure incidence, latency time to first seizure onset, number of seizure episodes, and their severity during observational period of 90 min. Number and duration of spike and wave discharges (SWDs) were determined in electroencephalogram (EEG). Seizure latency time was significantly shortened, while seizure incidence, number, and duration of HT-induced SWD in EEG significantly increased in rats receiving aminoguanidine 100 mg/kg before subconvulsive dose of HT. Aminoguanidine in a dose-dependent manner also significantly increased the number of seizure episodes induced by HT and their severity. It could be concluded that iNOS inhibitor (aminoguanidine) markedly aggravates behavioral and EEG manifestations of HT-induced seizures in rats, showing functional involvement of iNOS in homocysteine convulsive mechanisms.

Exercise decreases susceptibility to homocysteine seizures: the role of oxidative stress.

The aim of the study was to examine the effects of chronic exercise training on seizures induced by homocysteine thiolactone (HCT) in adult rats. Rats were assigned to: sedentary control; exercise control; sedentary+HCT; exercise+HCT group. Animals in the exercise groups ran 30 min daily on a treadmill for 30 consecutive days (belt speed 20 m/min), while sedentary rats spent the same time on the treadmill (speed 0 m/min). On the 31st day, the HCT groups received HCT (8.0 mmol/kg), while the control groups received vehicle. Afterwards, convulsive behavior and EEG activity were registered. Lipid peroxidation, superoxide dismutase (SOD) and catalase (CAT) activity were ascertained in the rat hippocampus. No signs of seizures were registered in sedentary and exercise control rats. Seizure latency was increased, while number of seizure episodes and spike-and-wave discharges (SWD) in EEG were decreased in the exercise+HCT compared to the sedentary+HCT group. Seizure incidence, the severity thereof and duration of SWDs were not significantly different between these groups. Exercise partly prevented increase of lipid peroxidation and decrease of the SOD and CAT activity after HCT administration. These results indicate beneficial effects of exercise in model of HCT-induced seizures in rats, what could be, at least in part, a consequence of improved antioxidant enzymes activity.

Ethanol suppressed seizures in lindane-treated rats. Electroencephalographic and behavioral studies.

This study examines the effects of ethanol on lindane-induced seizures in rats. The animals were divided into following groups: 1. saline, 2. DMSO (dimethylsulfoxide), 3. lindane dissolved in DMSO in the dose of 4, 6 or 8 mg/kg (L(4), L(6) and L(8) groups, respectively), 4. ethanol 2 g/kg administered 30 min prior to lindane (protected groups AL(4), AL(6) and AL(8)) and 5. ethanol alone (2 g/kg). In order to determine ethanol concentration in plasma, blood samples were collected by cardiac puncture 30 and 60 min after ethanol injection. For EEG and power spectra recordings, electrodes were implanted into the skull. The lindane treatment resulted in a dose-dependent increase of seizure incidence and severity. The rats displayed severe seizure patterns characterized by high voltage spike-wave complexes, poly-spikes and sleep-like patterns in EEG, while the power spectra were intensively elevated in comparison to the corresponding controls. Ethanol alone led to increased EEG power spectra, which became dominant in the range of 0-4 Hz. For evaluation of anticonvulsant ethanol action we compared latency to seizure, incidence and seizure severity (scale from 0 to 4) in the examined groups. Ethanol diminished seizure incidence in AL(4) and AL(6) groups, decreased intensity of convulsions, and prolonged duration of latency period in AL(8) group. We observed suppression of the EEG signs of lindane-provoked epileptiform activity in AL(4) and AL(6), but not in AL(8) group. These results suggest that ethanol acted protectively on lindane-induced seizures and suppressed behavioral and epileptic EEG spiking activity.

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.

Bovine haematological values during fattening with possible implications for muscle growth.

Haemoglobin concentration (Hb), haematocrit (PCV) and mean corpuscular haemoglobin concentration (MCHC) were determined as indicators of oxygen-carrying capacity in 25 Simmental bulls during intensive fattening. Their possible relations to muscle growth were also investigated. The animals were the progeny of two sires. Blood samples were taken at 6, 9, 12 and 15 months of age. After slaughter, the right thoracic rib cut (7-9) was dissected into the longissimus dorsi muscle (LD), other muscles (OM) and total muscles (TM) (LD+OM). There was a significant increase in the mean PCV and Hb values during fattening. The PCV and Hb values were significantly correlated with the tissue share of OM or TM only at 12 and 15 months of age. LD muscle share was not significantly correlated with any of the parameters at any fattening time. It would appear from these results that muscle growth proceeds in two phases. The first is until the age of 12 months and the other from then to maturity.

[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.

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.

[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.

Inhibition of metaphit-induced audiogenic seizures by APV in rats.

The influence of APV ((+/-)-2-amino-5-phosphonovaleric acid) on EEG activity and behavior was studied on a model of epilepsy induced by intraperitoneal administration of metaphit (1-(1-(3-isothiocyanatophenyl)-cyclohexyl)-piperidine). Male Wistar rats received an injection of metaphit (10 mg/kg) and were subjected to intense audio stimulation (100+/-3 dB, 60 s) at hourly intervals during the experiment. The seizures were classified according to a four point scale ranging from 0 (no seizure) to 3 (tonic convulsions). In our report we studied the time course which revealed the maximum incidence and severity of seizures 7-12 h after the injection (10 out of 12 rats, with severity of 2.25+/-0.32). APV (0.05, 0.1, 0.2 and 0.3 micromol) was injected intracerebroventricularly at the time of fully developed convulsions. APV inhibited seizures in a dose-dependent manner. The minimum dose, which completely blocked seizures in all animals, was 0.3 micromol, while ED50 were 0.11, 0.10 and 0.07 micromol against running, clonus and tonus, respectively. In contrast to behavioral inhibition of convulsions, metaphit-provoked epileptiform activity was not abolished by APV, and represented a prerequisite for the reappearance of behavioral seizures. It is suggested that APV is rather an anticonvulsant than an antiepileptic agent in this model of epilepsy.

The anticonvulsant potency of (+/-)-2-Amino-7-phosphonoheptanoic acid and (+/-)-2-amino-5-phosphonovaleric acid against metaphit-induced audiogenic seizures in rats.

Male Wistar albino rats were subjected to sound stimulation (100+/-3 dB, 60 s) at hourly intervals after intraperitoneal injection of metaphit (10 mg kg-1). The incidence and severity of audiogenic convulsions increased with time, reached a peak 7-12 h after metaphit administration (ten out of 12 and 2.25+/-0.32), and then gradually decreased until 31 h post-injection when no animal displayed signs of seizure. In order to test anticonvulsant activity on fully developed seizures, antagonists were delivered intracerebroventricularly after the 8th testing. The doses of AP7 were 0.005, 0.01, 0.02, 0.03 and 0.05 micromol, and 0.05, 0.1, 0.2 and 0.3 micromol of AP5, all in 5 microliters of physiological saline. Antagonists inhibited metaphit-induced audiogenic seizures in a dose-related fashion. The minimum doses that completely abolished convulsions were 0.03 and 0.3 micromol for AP7 and AP5, respectively. For suppression of running, clonus and tonus AP7 was 16-18 times more potent than AP5. These results indicate that AP7 is substantially more potent than AP5 against all phases of metaphit-induced audiogenic seizures in rats. (c) 1998 The Italian Pharmacological Society.

APH, an N-methyl-D-aspartate receptor antagonist, blocks the metaphit-induced audiogenic seizures in rats.

The effect of the competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, (+/-)2-amino-7-phosphonoheptanoic acid (APH) on electrocorticographic (ECoG) activity and behavior was studied in the model of epilepsy induced by systemic application of metaphit (1-(1-(3-isothiocyanatophenyl)-cyclohexyl)-piperidine). Male Wistar rats were injected with metaphit intraperitoneally (10 mg/kg, i.p.), and exposed to intense audio stimulation (electric bell generating 100 +/- 3 dB at animal level for 60 s) 1 h after administration and at 1-h intervals thereafter. ECoG tracings showed appearance of paroxysmal activity in form of spikes, spike-wave complexes and ECoG seizures. Audiogenic seizures consisted of wild running followed by clonic and tonic convulsions. Each behavioral seizure response had a characteristic ECoG correlate. The incidence and severity of seizures increased with time, reaching a peak 8-12 h after metaphit administration, and then gradually decreased until 31 h, when no animal responded to sound stimulation. APH was injected intracerebroventricularly (0.005, 0.01, 0.02, 0.03 and 0.05 mumol icv in 5 microL of sterile saline) after the 8th hour of audiogenic testing (AGS). APH inhibited seizures in a dose-dependent manner. The minimum dose which blocked seizures in all animals was 0.03 mumol. However, ECoG signs of seizure susceptibility were not suppressed by APH. After varying periods of time, behavioral seizures reappeared. It seems that APH blocks epileptiform propagation, but has less influence on the epileptogenic activity caused by metaphit.

[Dr. John Hughlings Jackson]. / Dr Dzon Hjulings Dzekson.

The great English neurologist, Dr. John Hughlings Jackson was born in Providence Green, Yorkshire, north England, in 1835. He spent his apprenticeship in the city of York, continued his medical education at St. Bartholomew's hospital in London, and qualified in medicine in 1856. After working in the city of York, he studied in London and in 1860 graduated at St. Andrews university in Scotland. He died in London in 1911, famous and celebrated by his colleagues as the "father of British neurology". Jackson was a prolific writer, witty and ingenious person, but also solitary and absent minded, with a lat of "tiny peculiarities of a genius". At first he was committed to become a philosopher but was persuaded by Jonathan Hutchinson, one of his rare friends, to enter medicine. His "Selected Writings" were first published in 1931 and reprinted recently, in 1996, by Arts & Boeve. Jackson, unlike William Richard Gowers, wrote his articles in a style which was not palatable to his contemporary colleagues. This could be the reason that his medical work was not widely known and would have remained in shadow had it not been rediscovered mostly by German neurologists, who preceded their English colleagues and collected the fame. Jackson gave the first classification of epileptic seizures acceptable, to a degree, even today. It was twofold: the first, taxonomic, which corresponds to contemporary classification of seizures, he compared to the attitude of a gardener who classifies flowers according to their beauty, height or color, and was aware of its purely phenotypic, descriptive and utilitarian character; the second was scientific, physiologic and it would correspond nowadays to the current concept of syndromic classification. Jackson was aware that this 'scientific classification' was to await for the future time, when the knowledge of the real nature of epilepsy became fundamentally broadened. On the other hand, he thought that all the epilepsies were partial becoming generalized only secondarily. Partial epilepsies were the starting point in his work. He realized that epileptic attacks are not different types of epilepsies with different pathophysiological mechanisms, but that they differ in respect to the focus of origin; he stressed their gray matter (cortical) arigin with the cause located as the rule "on the side of the brain, opposite to the body convulsed". Jackson's ideas on epileptogenesis and the localization of epileptogenic processes represent his fundamental contribution to the understanding of their pathophysiology. His most philosophical contribution to neurology was the concept of the evolution and dissolution of the nervous system, which was the consequence of his ideas on its organization. Symptoms observed after the lesion of a certain part of the brain are not the consequence of its function; they are the result of the function of the remaining non-lesioned regions which are in a certain way freed from the adjacent or a higher control. This concept of interpretation af the symptoms of the nervous diseases remains applicable even today. Jackson was the first to stress the importance of ophthalmoscopy in neurology in all cases of neurologic disease, especially in cases of optic neuritis (papilloedema) which may be present even if the patient did not notice the minimized visual acuity. The way of thinking that Jackson introduced in medicine and neurology may be his most precious legacy to the generations that followed.

[Dr. John Baptiste Edouard Gélineau]. / Doktor Zan Baptist Eduar Zelino.

With this brief review we honor the memory of the great French doctor Jean Baptiste Edouard Gélineau. Dr. Gélineau was born on December 23, 1828 at Blaye, Gironde, close to the Bordeaux region. His name is connected with the first clinical description of the disease for which he, both by the right of the primacy as well as ad valorem of his first two names, coined the name "narcolepsy". He was the first to notice the intrinsically evanescent symptoms of narcolepsy, such as excessive daytime somnolence, imperative sleep habits and cataplexy or "astasia" as he called it, and incorporate them into a single clinical syndrome. In 1881 Gélineau discussed Kaffe's case of "maladie du sommeil" as a proof of the existence of the new disease described a year before. As a good clinical observer Gélineau noticed the close relation of emotional engagement and astasia. His attitude was that narcolepsy was a nosologic entity, a disease sui generis, but admitted that it could appear purely as a symptom only. This was in discordance with the views in England where (in 1928) Dr. Samuel Alexander Kinnier Wilson repudiated such convictions; in 1930 Lhermitte still shared the same opinion. Gélineau differentiated narcolepsy from epilepsy with the elegance of clinical reasoning. Overall, Gélineau described three elements of the narcoleptic pentade. Sleep paralyses were first described by Mitchell in 1876, and were first attributed to narcolepsy by Wilson in 1928; in 1930 Lhermitte first described hypnapompic, and Daniels, in 1934, hypnagogic sleep paralysis. Hypnagogic hallucinations were described by Maury in 1848 and subsequently by de Saint Denis in 1867. In twenties they were thoroughly studiesed during the epidemic encephalitis and after the Big War in 1922 by Levy. The life story of Dr. Gélineau covers multivarious activities. As a young student of the Rochefort Navy Medical School he took part in the fight against colera which deluged the city of La Rochelle. In 1849 he became the "Intern" of the Navy Hospital and next year a "Surgeon of the Third Class". As a Navy surgeon he visited French colonies in the Indian ocean: first the Reunion island and then Mayotte island of the Commores Archipelago. Of this period he wrote "Voyage a i'lle de la Réunion", memoirs published much later, in 1905, in which he described colonial life and abolition of slavery. The story of Elise, a beauteous Creole woman, a concubine of a young naval Commander, who delivered a child that soon died, inexorably points to the autobiographic character of his work. He defended a doctoral thesis "Aperçu Medical de I'lle de Mayotte" at Montpellier University School of Medicine in 1858, using the data collected during his year-and-a-half stay on a Mayotte island; at that time he was a "Navy Surgeon of the Second Class". For his dedication in fighting against epidemics that broke out during the French-German war in 1870 he was nominated for the Legion of Honor, but received it only later. In 1871 Gélineau introduced "Doctor Gélineau's tablets" for the treatment of epilepsy (contained bromide and arsenic). He was a member of the Société de Médicine, Société d' Hypnologie, La-Société Française d' Hygiène, and a few others. After retirement at the age of 72, Gélineau switched to wine production, continuing the family tradition; for the quality of his Bordeaux wines he was awarded gold medals at the Anvers and Paris Exhibitions. Dr. Gélineau died on March 2, 1906, at Argeles Gazost in Pyrnees honored by the titles of Chevalier de la Légion d' Honneur, Officier d'Academie and Commander of Nichan of the Ottoman Empire.

Possibility of blocking n. ischiadicus within foramen ischiadicum majus in sheep.

The blocking of the ischiadic nerve within foramen ischiadicus majus of 8 sheep was performed with 6-12 ml 2% xylocain from three different places: 1. From the middle of a line joining the top of processus spinosus of the 1st sacral vertebra and the peak of trochanter major. The needle pierces vertically through the skin, gluteal fascia and m. gluteus medius till foramen ischiadicum majus. 2. Along the most prominent part of crista iliaca on the gluteal surface of ala ossis ilium along the medial side of well expressed linea glutea. The needle pierces by an angle of 45 degrees through the skin, gluteal fascia and m. gluteus medius till the nerve itself. When the nerve is touched the animal makes a jerk. 3. Along the caudal part of tuber sacrale with the needle orientated caudo-ventro-laterally through the skin, gluteal fascia and m. gluteus medius toward foramen ischiadicum majus. The most appropriate approach for blocking is along crista glutea on the gluteal surface of ala assis ilii. In this approach the success is complete. The symptoms of the blocking appear immediately after the application. The complete akinesia of the limb appears 15 minutes after the application of 6 ml, and 5-10 minutes after being applied 12 ml of 2% xylocain. The blocking symptoms disappear within 90-100 or 120-140 minutes. Beside the blocking of n. ischiadicus, a simultaneous blocking of n. gluteus cranialis, n. caudalis and n. cutaneus femoris caudalis as well was performed within foramen ischiadicus majus.

[Eponyms and epilepsy (history of Eastern civilizations)]. / Eponimi i epilepsija (istorijat istocnih civilizacija).

The history of eponyms for epilepsy in the lands of the Eastern globe present the portrait of the attitudes of both the laymen and skilled people towards the disease and patient, as well as to the Nature itself. As opposed to the West which during the Middle ages changed its concepts of epilepsy as the organic brain disease for the sublime 'alchemic' position, the people of the East were more prone to consider from the beginning of their civilization till the XIX century that epilepsy is the consequence of the evanescent spiritual and extracorporal forces which by themselves were out of their reach. As compared to the western civilization, the historical resources are, often as a consequence of a linguistic barriers, more scarce-as consequently is the number of eponyms, but are nevertheless picturesque. The medical science from Babylonian period presumed that epileptic manifestations are the consequence of the demonic or ill spiritual actions. There existed an attitude that at the beginning of an epileptic attack the patient was possessed by a demon (the Akkadic, i.e., Babylonian verb "sibtu" denoting epilepsy, had the meaning "to seize" or "to be obsessed"); at the end of the clonic phase the demon departed from the body. Different demons were responsible for different forms of epilepsy such as nocturnal and children epilepsy, absence epilepsy and pure convulsions, simple and complex automatisms, and gelastic epilepsy. Thus, the doctors from the period of Babylon aside from making primordial classification of epilepsies, knew about their clinical picture (prodromal symptoms and aura, Jackson's epilepsy. Todd's paralysis), postictal phenomena and intericatl emotional instability; provocative factors were also known (sleep deprivation, emotions, as well as alcohol, albeit in a negative sense-as a cure for epilepsy). There is no doubt than in the period of Babylon the clinical picture of serial fits and its progress to status epilepticus were clearly recognized and considered as life threatening events. Persian history of epilepsy, except from the 6th century Zoroastrian "Avesta" document, lacks the written or spoken medical heritage untill the 7th century A.D. and the Arabic conquest of the entire Moslem world. On the other hand, Islamic medicine should be freed from the simple prejudice that the Moslem authors were only the translators of Greek medicine; contrary to such a view, their work contains a high degree of individuality. Although Mohammed introduced a lot of novelty into medicine, Khoran and the Sayings do not explicitly refer to epilepsy. Of importance is to notice that Moslem medicine did not have demons in the "repertoire" of direct causes of epilepsy. The causes and the cures of epilepsy were more magic-mystical and occult in nature, which is reminiscent of the European, as well as Serbian Middle age attitudes. Avicenna recognized difference between children and adult epilepsy. He considered insomnia and afternoon siesta as well as intensive sounds and light to be a provocative factors, whereby we see that at least empirically he knew of sleep (deprivation), startle and reflex epilepsy. The XIII century invasion of Mongols brought about the recession in Moslem Medicine; it recovered only in the XVIII century under the strong influence of European medicine handed over to us through Jewish doctors of various nationalities. The story of the China history of epilepsy has its debut approximately in the 8th century B. C. Medical texts from this period name epilepsy "Dian" and "Xian" which meant "the falling sickness" and "convulsions", respectively. Chinese medical terminology often interchangeably used the words "mania", "madness" and "psychosis" for "epilepsy" which, aside from a prominent language barrier, brings additional confusion. Although Chinese documents gave the first description of the grand mal epileptic attack already in the 8th century B. C. (ABSTRACT TRUNCATED)

[Epilepsy, eponyms and patron saints (history of Western civilization)]. / Epilepsija, eponimi i pokrovitelji (istorijat zapadnih civilizacija).

From a historic point of view, epilepsy and its eponyms were in an ontogenetic symbiosis throughout their history. Epilepsy is a disease with a history of eponyms presenting the frame of mind of both streetwise as well as skilled "authors" about its origin and nature. From ancient times the names for epilepsy, archetypal Hippocratic disease, just as rich in number as varied in their implication, reflected the local folkways of thinking. In this article we briefly presented more than 50 eponyms and patrons of epilepsy. As the source of information we used both the apocryphal, canonical and hagiographic as well as heretic literature, legends and iconography from the Middle Ages of domestic and foreign origin. Pre- and post-Hippocratic era, apart from stemming from the oldest written medical sources, point to the position that the disease had organic origin located in the brain. The period of Rome adopted the attitudes set by Galen which remained en vogue throughout the emerging Middle Ages and Renaissance. These eras generated new eponyms which reflected a downfall in the manor, stating that the disease is the consequence of supernatural forces. In the "Age of darkness" eponyms for epilepsy reflected more the relation of men to the Nature than to the disease or a sick man; this is evidenced through the generation of number of patrons for the disease. The most famous patron of patients with epilepsy was St. Valentine (after conversion from pagandom he died in Rome as a martyr, c. 270). He was allotted a patronage either due to the phonic resemblance of his name with the (past participle of the) verb "fallen"-as Martin Luther claimed, or due to a cure of epilepsy of the son of a Roman rhetor who built for him a chapel in which he continued to cure the sick. The emergence of a flamboyant personality of Paracelsus on the historic scene of the XVI century represents a less successful attempt to revoke the way of thinking set by the old Greek doctors; however, it brought about the precipitous decay of attitudes that started with Romans and inaugurated the way of thinking characteristic of Renaissance and the ages thereafter. Serbian literature of the Middle Age was strongly impacted by influences that fanned from Italy (Salerno) and south France (Montpellier), reflecting the attitudes of medical schools and universities prevailing at that time Europe. The name [symbol: see text] from Hilandar Medical Codex No 517 (XV-XVI century) is obviously taken from Byzantine medicine, which was founded on the works of Hippocrates, Galen and Dioscurides. It came down to us through the Serbian folk Byzantine codices named "latrosophia of Hilandar", preserved mostly from the author Michail Pselos (XI century). On the other hand, the name [symbol: see text] or morbus magnus, reflects its Roman origin. The name [symbol: see text] meaning fainting, loss of consciousness or syncope, stems from the same source. The name [symbol: see text] designated epileptic disease in Serbian monks, monasteries probably being the only niche where epileptics could find refuge. Children's epilepsy or convulsions are expressed as [symbol: see text] No mention is found of epileptic status except for the notion [symbol: see text] meaning "to be without consciousness for a longer period of time'; it does not, however, refer directly to epilepsy or convulsions. It is worthy noting that already in the XIV century Serbs had their medical literature translated to their own language, and were the only one of all Slavic peoples that did so. Nevertheless, both apocryphal and canonical, as well as consecrated medicine were based on magic, astrology and occultism. The magic formulas used in Middle Age Serbia for the cure of epileptics as well as sick in general, were basically irrational; still, as a trace of its descension they contained unintelligible words of the eastern origin (Greek, Persian or Jewish). (ABSTRACT TRUNCATED)