Prevalence of illicit drug use among medical students in Northern Greece and association with smoking and alcohol use.

AIM: The aim of this study was to estimate the prevalence of illicit drug use among medical students in Northern Greece, to identify the motivations for cannabis use and also to investigate the possible associations with smoking and alcohol misuse. METHODS: A sample of undergraduate students completed an anonymous, self-administered, web-based survey assessing lifetime and past-year illicit substance use. To further evaluate the motivation to use, the responders were classified into three subtypes (self-medication, recreational, and mixed). The CAGE questionnaire and a question assessing binge drinking were also used. Illicit substance use was correlated with age, gender, study year, CAGE and binge drinking. RESULTS: Five hundred and ninety-one undergraduate medical students completed the survey. The lifetime prevalence of illicit drug use was 24.7 %, while the most used drug was cannabis (22.2 %). The past-month prevalence of cannabis use was 8.1 %. Experimentation was the predominant reported motivation for its use, and the recreational subtype was the most prevalent. Binge drinking behavior was reported by 22.7 % of the sample, and the CAGE screening test was positive for 6.4 % of the students. Most students (80.4 %) characterized themselves as non-smokers. In the multivariate analysis, lifetime use of illicit drugs was significantly correlated with smoking and binge drinking. No associations were found with gender, age, study year or CAGE. CONCLUSION: Smoking and binge drinking were found to be risk factors for illicit drug use, whereas no association was found with gender, age, study year and CAGE. HIPPOKRATIA 2017, 21(1): 13-18.

Increased CD14+ and decreased CD14- populations of monocytes 48 h after zolendronic acid infusion in breast cancer patients.

It has been proposed that bisphosphonates cause osteonecrosis of the jaws through impairment of the monocyte population function and proliferation. Such changes have been confirmed in jaw tissues, ex vivo. In this clinical study, we report for the first time a similar pattern of changes in peripheral blood monocytes. INTRODUCTION: The aim of this study is to examine the effect of zolendronic acid administration in the peripheral blood white cell population, seeking a plausible pathophysiological link between bisphosphonates and osteonecrosis of the jaw. METHODS: Twenty-four breast cancer patients, under zolendronic acid treatment for bone metastasis, were included. Peripheral blood samples were obtained prior to and 48 h following zolendronic acid administration. Flow cytometry gated at leukocyte, monocyte, and the granulocyte populations for the CD4/CD8/CD3, CD3/CD16+56/CD45/CD19, CD14/CD123, and CD14/23 stainings were performed. RESULTS: We were able to record a number of changes in the white cell populations after 48 h of zolendronic acid administration. Most importantly, in the monocyte populations, we were able to detect statistically significant increased populations of CD14+/CD23+ (p = 0.038), CD14+/CD23- (p = 0.028), CD14+/CD123+ (p = 0.070, trend), and CD14+/CD123- (p = 0.043). In contrast, statistically significant decreased populations of CD14-/CD23+ (p = 0.037) and CD14-/CD123+ (p = 0.003) were detected. CONCLUSIONS: Our results provide evidence supporting the hypothesis that bisphosphonate administration modifies the monocyte-mediated immune response. An increase of CD14+ peripheral blood monocyte (PBMC) populations along with a decrease of CD14- PBMC populations has been recorded. The latter finding is in accordance with limited-currently existing-evidence and warrants further elucidation.

The Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) questionnaire: cultural adaptation and validation of the Greek version.

AIM: To adapt cross-culturally the Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) for use in Greek patients with atrial fibrillation (AF) and to evaluate its psychometric properties. METHODS: Professional translators were involved in the inverse translation procedure. Twenty patients with AF participated in the cultural adaptation procedure. One hundred two consecutive patients participated in the validation process that included reliability (internal consistency, test-retest reliability) and validity assessment (face validity, construct validity). RESULTS: Greek AFEQT showed high internal consistency (Cronbach's alpha for overall scale: 0.97, subscales: Symptoms: 0.90, Daily Activities: 0.93, Treatment Concern: 0.91, Treatment Satisfaction: 0.83) and test-retest reliability (Spearman's rho: 0.99, p <0.001, Wilcoxon's test, p =0.959). Face validity was rated with a median of 7 by the patients. Finally, Greek AFEQT showed appropriate construct validity of demonstrating adequate convergent validity with the moderate to strong correlations of AFEQT domains with the Physical and Mental Component Summaries of SF-12 (Spearman's rho: 0.53-0.78, p <0.001). CONCLUSIONS: The Greek version of AFEQT has shown good psychometric properties and can be a useful tool in future studies on the quality of life of patients with AF. Hippokratia 2016, 20(4): 264-267.

Leptin increases luteinizing hormone secretion of fasting female rats.

PURPOSE: To investigate whether leptin acts directly on the anterior hypophysis by influencing gonadotropin secretion in vivo. MATERIALS AND METHODS: Cycling female rats were catheterised for frequent blood sampling and were either fasted or allowed free access to food. Stereotactic lesion of the medial preoptic area (MPOA) of the hypothalamus was performed in order to eliminate gonadotropin releasing hormone (GnRH) production. Leptin was administered at a dose of one mg/kg i.v. and blood samples were taken just before leptin administration and then after 30, 60, 90, 120, and 180 minutes. Plasma gonadotropin levels were determined. With completion of sampling, the brains were removed and the localisation of the lesions was verified histologically. RESULTS: Leptin at one mg/kg induced an increase in luteinizing hormone (LH) secretion in fasting rats, both in those with a lesion and those with intact medial preoptic area with a peak occurring 90 minutes after infusion. The augmenting effect was more prominent when the hypothalamus was intact. There was no effect in fed animals with or without lesion. Similarly, no effect was observed on follicle stimulating hormone (FSH) levels in any of the experimental groups. CONCLUSIONS: Leptin acts directly on the hypophysis enhancing LH but not FSH secretion. Nutritional state influences leptin's effect on the hypothalamus and the hypophysis.

Effect of ropivacaine infiltration on muscle regeneration: a morphometric analysis.

BACKGROUND/AIM: Local anaesthetic myotoxicity is a well described phenomenon resulting in reversible muscle damage. Considering that in previous studies microscopic images were evaluated without quantification of morphologic characteristics, the aim of the present study was evaluate muscle regeneration after local anaesthetic infiltration. MATERIALS AND METHODS: Wistar rats underwent injection of the left tibialis anterior muscle with ropivacaine (0.75%, group HC or 0.375%, group LC), while the contralateral muscle was injected with saline (group SL). Six weeks later, the muscles were dissected, stained using acid ATPase and examined under light microscope coupled with a computer imaging system for morphometric analysis. Sections were evaluated regarding the content of different muscle fibre types (type I, IIa and IIb), fibre cross-section area and perimeter. RESULTS: Groups were comparable regarding the ratio of different muscle fibre types. Regenerated type I fibres of both HC and LC groups had significant greater mean cross-sectional area and perimeter, compared to SL fibres. No signs of necrosis or inflammation were observed. Type IIa and IIb fibres didn't show significant differences. CONCLUSIONS: Regenerated muscles, following local anaesthetic application, showed long-term morphological differences, which could lead to impaired function. Further studies are needed, in order to clarify the underlying cellular mechanisms and the subsequent possible functional impairment.

Efficacy, safety and tolerability of green tea catechins in the treatment of external anogenital warts: a systematic review and meta-analysis.

BACKGROUND: External anogenital warts (EGWs) are non-malignant skin tumours caused by human papillomavirus. They are one of the fastest growing sexually transmitted diseases. Current treatments are unsatisfactory. Green tea sinecatechin Polyphenon E ointment is a botanical extract from green tea leaves exhibiting anti-oxidant, anti-viral and anti-tumour properties. OBJECTIVE: The aim of this study was to integrate valid information and provide basis for rational decision making regarding efficacy and safety of green tea extracts in the treatment of EGWs. METHODS: A systematic search in electronic databases was conducted using specific key terms. Main search was performed independently by two reviewers. The accumulated relevant literature was subsequently systematically reviewed and a meta-analysis was conducted. RESULTS: Three randomized, double-blind, placebo-controlled studies evaluating efficacy and safety of Polyphenon E 15% and 10% in the treatment of warts were included in the systematic review and meta-analysis. A total of 660 men and 587 women were enrolled. Regarding primary outcome, both Polyphenon E 15% and 10% demonstrated significantly higher likelihood of complete clearance of baseline and baseline and new warts compared with controls. No significant heterogeneity was detected. Recurrence rates were very low. Commonest local skin sign was erythema and local skin symptom was itching. CONCLUSIONS: Efficacy of Polyphenon 15% and 10%, at least for the primary endpoint, is clearly indicated. Polyphenon E treatment exhibits very low recurrence rates and appears to have a rather favourable safety and tolerability profile. Recommendations for future studies should include evaluation of the efficacy of green tea catechins in the treatment of internal anogenital warts and direct comparison with its principal comparator, imiquimod.

Gabapentin and pregabalin in the treatment of fibromyalgia: a systematic review and a meta-analysis.

WHAT IS KNOWN AND OBJECTIVES: Fibromyalgia (FBM) is a common chronic pain disorder affecting up to 2% of the general population. Current treatment options are mostly symptom-based and limited both in efficacy and number. Two promising alternatives are gabapentin (GP) and pregabalin (PB). We aimed to estimate the efficacy and safety/tolerability of the two compounds in FBM through a systematic review and a meta-analysis of relevant randomized double-blind placebo-controlled (RCT) were performed. DATA SOURCES, EXTRACTION AND ANALYSIS: A literature search was conducted through MEDLINE, EMBASE, Cochrane CENTRAL and the reference lists of relevant studies. Responders to treatment (>30% reduction in mean pain score) and dropouts due to lack of efficacy were used as primary outcome measures. Dropout rates and incidence of common adverse outcomes were also investigated. Four RCTs, reporting data on 2040 patients, were reviewed and three of them using PG were included in the meta-analysis. RESULTS: Pregabalin at a dose of 600, 450 and 300 mg per day is effective in FBM compared to placebo (NNT: 7, upper 95% CI: 12, 450 mg). A number of adverse events (AE), such as dizziness, somnolence, dry mouth, weight gain, peripheral oedema, is consistently associated with treatment at any dose and could lead one out of four patients to quit treatment (NNH: 6, lower 95% CI: 4, 600 mg). Indirect comparison meta-analysis suggests that PB at a dose of 450 mg per day could result in more responders than at 300 mg, but this result needs to be interpreted with caution as there were no significant differences between 600 and 300 mg or between 600 and 450 mg. Data on GP is limited. WHAT IS NEW AND CONCLUSIONS: The analysis indicates that PB at a dose of 450 mg per day is most likely effective in treating FBM, although AE are not negligible. Further evidence is necessary for more conclusive inferences.

A2delta ligands gabapentin and pregabalin: future implications in daily clinical practice.

Gabapentin (GP) and pregabalin (PB) are structurally related compounds and their predominant mechanism of action is the inhibition of calcium currents via high-voltage-activated channels containing the a2d-1 subunit. A2delta ligands are approved for the treatment of pain of diabetic neuropathy and post-herpetic neuralgia in adults and as adjunctive therapy of partial seizures in children. Recently, pregabalin has been approved for treatment of anxiety disorders in Europe. Besides their already approved indications both drugs are promising treatment options for a number of different serious and debilitating diseases, as fibromyalgia, neuropathic pain of spinal cord injury, hot flushes, and essential tremor. In the present review, the unique mechanism of action of the above drugs is critically analyzed and evidence for their future use is provided. Gabapentin and pregabalin can be treatment options for these disorders, however, a clear comparison between the two drugs can not be performed, since there is no direct comparison study. The most common side effects are dizziness and somnolence which are also the most frequent reasons for withdrawal. Recommendations for future studies should include assessment of ideal titration period for GP and PB to reduce incidence of somnolence and dizziness and increase tolerability, cost-effectiveness and dose-response analysis of PB and GP and direct comparison of the two drugs.

PDE5 inhibitors: in vitro and in vivo pharmacological profile.

PDE5 inhibitors have been clearly established as first-line therapy for the treatment of erectile dysfunction (ED). Three PDE5 inhibitors--sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis)--are currently approved by the FDA and the EMEA for use in ED, whereas sildenafil is also marketed under a different proprietary name (Revatio) for the treatment of pulmonary arterial hypertension (PAH). A forth PDE5 inhibitor, udenafil (Zydena), is currently marketed. In the present review the molecular basis and the mechanism of action of PDE5 inhibitors is discussed. In addition experimental and clinical data concerning their effects on different tissues, organs and systems is systematically reviewed and their possible beneficial action in numerous disorders is presented.

The effect of intra-abdominal hypertension alone or combined intra-abdominal hypertension-endotoxemia in cerebral oxygenation in a porcine model.

BACKGROUND: Abdominal compartment syndrome (ACS) has been recognized as an entity, affecting cardiovascular, pulmonary, and cerebral function, while it is often complicated with sepsis. Goal of the study was the evaluation of brain oxygenation during ACS alone and in combination with endotoxinemia. MATERIALS AND METHODS: Sixteen pigs, undergone intra-abdominal hypertension, were allocated to receive intravenous administration of either saline or endotoxin. Pigs were evaluated regarding brain tissue oxygenation (PbrO2), systemic oxygenation (PaO2) and regional cerebral blood flow (rCBF). RESULTS: Statistical analysis revealed significant reduction of PbrO2 over time for sepsis group, after endotoxin administration. Regarding differences between groups, sepsis group experienced lower PbrO2 values, compared to saline group, only after endotoxin administration. Both groups experienced reduction in arterial oxygenation, with greater pertubations seen after sepsis induction. Regarding rCBF, septic pigs showed greater flow values, while ACS alone did not influence rCBF. ACS has no deleterious effects in cerebral oxygenation and flow, provided systemic oxygenation and CPP are maintained above normal value. CONCLUSIONS: Combined sepsis-ACS lead to perturbations in cerebral oxygenation, in conjunction with greater rCBF values. The latter could be ascribed to abnormalities in oxygen extraction.

Effects of oral phentolamine, taken before sleep, on nocturnal erectile activity: a double-blind, placebo-controlled, crossover study.

The objective of this study was to determine the effects of oral phentolamine, administered before sleep, on nocturnal penile erectile activity of men with mild to moderate erectile dysfunction (ED). We studied five patients with mild to moderate ED (mean age 34.8 +/- 8.13 and mean duration of ED 31.8 +/- 23.5 months), in a double-blind, placebo-controlled, crossover study. All patients received oral phentolamine (Vasomax) at a dose of 40 mg and placebo for three consecutive nights respectively and were submitted to nocturnal penile tumescence and rigidity monitoring (NPTR) with the Rigiscan device. NPTR parameters of the two 3-night recordings were evaluated and compared. Administration of oral phentolamine before sleep was associated with a statistically significant increase in the number of erectile events with rigidity > or = 60% lasting > or = 10 min (P = 0.02), as well as the rigidity activity units (RAU) value per hour sleep, both at the base (P = 0.023) and the tip of the penis (P = 0.019). The number of events as measured by Rigiscan software (20% change in circumference), as well as tumescence activity units (TAU)/h values did not show any statistical difference. No adverse effects were recorded. It is concluded that oral phentolamine administered before sleep enhanced NPTR parameters associated with the quality of the erectile events. Such results provide a pathway for the development of a prevention strategy for ED. Future studies will elucidate whether vasoactive agents taken on a regular basis before sleep, can prevent ED in men at risk, protecting also minimally and moderately impotent patients to become moderately and severely impotent respectively.

Peripheral chemoreceptor activation enhances 5-hydroxytryptamine release in the locus coeruleus of conscious rats.

Intravenous bolus injection of KCN (40 microg) elicited brief but pronounced tachypnea, bradycardia and pressor response, and led to a 37% increase in 5-hydroxytryptamine (serotonin) (5-HT) release in the locus coeruleus (LC) of freely moving rats. Slow infusion of KCN (15 microg/min) for 10 min induced only a slight pressor response, but increased the respiration rate (+39 breaths/min), as well as 5-HT release in the LC (+60%) throughout the infusion. In rats with transected chemoreceptor afferents, neither injection or infusion of KCN changed 5-HT release, suggesting that in intact animals, the effect on extracellular 5-HT was due to activation of peripheral chemoreceptors. In summary, we report that peripheral chemoreceptor activation enhances 5-HT release in the LC, indicating that 5-HT might be involved in the modulation of LC activity by ascending chemosensory information.

Release of glutamate and GABA in the amygdala of conscious rats by acute stress and baroreceptor activation: differences between SHR and WKY rats.

To reveal the functional importance of amino acid neurotransmission in the amygdala (AMY) of conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, the in vivo release of glutamate (GLU) and GABA in this brain structure was studied using the push-pull superfusion technique. Basal GLU and GABA release rates in the AMY were comparable in SHR and WKY rats, although arterial blood pressure (BP) in SHR (152+/-6 mmHg) was higher than in WKY rats (102+/-4 mmHg). Neuronal depolarization by superfusion with veratridine enhanced the release of GLU and GABA to a similar extent in both rat strains. On the other hand, exposure to noise stress (95 dB) for 3 min led to a tetrodotoxin-sensitive increase in GLU release in the AMY of SHR, but not WKY rats. The concurrent pressor response to noise was enhanced in SHR as compared to WKY rats. A rise in BP induced by intravenous infusion of phenylephrine for 9 min had no effect on amino acid release in the AMY of both strains. The data suggest an exaggerated stress response of glutamatergic neurons in the AMY of SHR as compared with WKY rats, which might be of significance for the strain differences in the cardiovascular and behavioural responses to stress. The results also show that, in both rat strains, glutamatergic and GABAergic neurons in the AMY are not modulated by baroreceptor activation. Moreover, hypertension in adult SHR does not seem to be linked to a disturbed synaptic regulation of glutamatergic or GABAergic transmission in the AMY.

Effects of inescapable shock and conditioned fear on the release of excitatory and inhibitory amino acids in the locus coeruleus.

We investigated the importance of endogenous amino acids in the locus coeruleus in inescapable electric shock and conditioned fear. In naive rats and in rats exposed to noise (N), light (L) and electric shock (S) or to N + L only, the locus coeruleus was superfused with artificial cerebrospinal fluid through a push-pull cannula and the release of GABA, taurine, glutamate, aspartate, serine and glutamine was determined in the superfusate by HPLC after derivatization with o-phthaldialdehyde. Locomotor activity, arterial blood pressure and heart rate were telemetrically monitored. The placement of naive rats or conditioned rats from their home cage to a chamber provided with a grid-floor for shock virtually did not change the release rates of the amino acids in the locus coeruleus. Motility was enhanced in naive and conditioned rats to a similar extent. Blood pressure and heart rate were enhanced in conditioned rats only. Exposure to N + L + S for 5 min greatly enhanced the release rates of all determined amino acids in the locus coeruleus. In conditioned rats the increase in release of most amino acids lasted longer than in naive rats. Electric shock also enhanced motility, blood pressure and heart rate. In conditioned rats, motility and cardiovascular changes were more pronounced and/or lasted longer than in naive rats. Exposure of conditioned rats to the conditioned stimuli N + L for 5 min led to an increased release of taurine and aspartate. The enhanced release of taurine lasted 30 min. Exposure to N + L did not affect the release rates of amino acids in naive rats. N + L did not influence motility but arterial blood pressure and heart rate were elevated in conditioned rats. The findings show that inescapable electric shock enhances the release of several amino acids in the locus coeruleus, while conditioned fear selectively increases the outflow of taurine and aspartate. Moreover, conditioned fear prolongs the response of excitatory and inhibitory amino acids to electric shock. The results suggest that an excitatory amino acid (aspartate) and an inhibitory amino acid (taurine) of the locus coeruleus are implicated in conditioned fear.

A study of the effect of benzylpenicillin on isolated human gallbladder.

The contractile effect of benzylpenicillin on isolated rings of human gallbladder was studied using preparations taken from surgical specimens after gallbladderectomy. The gallbladder was cut into two pieces and one ring was cut from each piece; one ring was mounted in a 100 ml organ bath containing Krebs solution and the isotonic changes of the preparation were recorded for each experiment. Benzylpenicillin (1 x 10(4) to 1 x 10(8) IU/l) was shown to exert a dose-dependent contractile effect on isolated human gallbladder rings which was blocked by atropine (1 x 10(-8) M). The benzylpenicillin-induced contractile effect was analogous to contraction observed with acetylcholine (1 x 10(-7) to 1 x 10(-2) M). The effect of benzylpenicillin on isolated human gallbladder may reflect a possible decrease in gallbladder emptying time in vivo, suggesting a beneficial effect of benzylpenicillin in antimicrobial treatment of gallbladder infections.

Histological changes and neurotransmitter levels three months following perinatal asphyxia in the rat.

The involvement of excitatory amino acids (EAA) in the pathogenesis of hypoxic-ischemic states is well-documented. Information on the role of overexcitation by EAA in perinatalasphyxia (PA), however, is limited and data from adult models cannot be directly extrapolated to immature systems. Moreover, most adult models of ischemia are representing stroke rather than PA. We decided to study long term effects in a non-invasive rat model of PA resembling the clinical situation three months following the asphyctic insult. Morphometry on Nissl - stained sections was used to determine neuronal death in frontal cortex, striatum, hippocampus CA1, hypothalamus and cerebellum L1, and the amino acids glutamate, glutamine, aspartate, GABA, taurine, arginine as well as histamine, serotonin and 5-hydroxy-indoleacetic acid were determined in several brain regions and areas. Morphometry revealed that neuronal loss was present in the hippocampal area CA1 in all groups with PA and that morphological alterations were significantly higher in the cerebellar granular layer. The prominent light microscopical finding in all areas of asphyctic rats studied was decreased Nissl-staining, suggesting decreased cellular RNA levels. Glutamate, aspartate and glutamine were significantly elevated in the hypothalamus of asphyctic rats probably indicating overstimulation by EAA. Excitotoxicity in this area would be compatible with findings of emotional / behavioral deficits observed in a parallel study in our model of PA. Our observations point to and may help to explain behavioral and emotional deficits in Man with a history of perinatal asphyxia.

Time course of isolated rat fundus response to muscarinic agonists: a measure of intrinsic efficacy.

The establishment of a dose-response relationship and its quantification is the usual procedure for analysing drug action on an isolated organ. However, the time course of the effect seems to be an inherent characteristic of the agonist which produces it. In our study, we have analyzed the time-response curves of four cholinergic agonists (acetylcholine, methacholine, carbachol and bethanechol) which produce tonic contractions of the isolated rat gastric fundus. The order of affinity of agonists to muscarinic receptors on the rat fundus were carbachol > bethanechol > methacholine > acetylcholine (K(A) values: 46 +/- 12, 84 +/- 21, 380 +/- 110 and 730 +/- 120 nM, respectively). The effective concentrations which produced 60% of the maximal response (EC60) were used for establishing the time-response curves. The time-response curves were also recorded after partial alkylation of muscarinic receptors with phenoxybenzamine, after exposure of the isolated rat fundus to physostigmine and after addition of supramaximal concentrations of the agonists. The experimental time-response curve for acetylcholine was on the extreme left, followed by curves for methacholine, bethanechol and carbachol, respectively. Phenoxybenzamine and supramaximal doses of the agonists did not change the order of response development in time, but supramaximal doses shifted all curves to the left and phenoxybenzamine shifted all time-response curves to the right. Only physostigmine shifted the time-response curve for methacholine to the right. The results of our study suggest that the response rate of the isolated rat gastric fundus to cholinergic agonists depends on the intrinsic activity of these agents, but not on their affinity for muscarinic receptors.

The release of inhibitory amino acids in the hypothalamus is tonically modified by impulses from aortic baroreceptors as a consequence of blood pressure fluctuations.

We investigated in conscious, freely moving rats whether the release of GABA, taurine and arginine in the hypothalamus is influenced by impulses originating from peripheral baroreceptors. The posterior hypothalamic nucleus was superfused with artificial cerebrospinal fluid through a push-push cannula and the release of amino acids was determined in the hypothalamic superfusate of control rats, as well as of rats after bilateral aortic denervation (AD). AD led to hypertension and increased the lability of arterial pressure. In sham-operated rats, intravenous infusion of phenylephrine increased blood pressure and the hypothalamic release of GABA and taurine. AD almost abolished the phenylephrine-induced release of the inhibitory amino acids. Similarly, the pressor response to hypervolaemia, elicited by blood injection, enhanced the release rates of GABA and taurine only in sham-operated rats. Baroreceptor unloading evoked either by intravenous infusion of nitroprusside, or by haemorrhage, decreased the release rates of GABA and taurine in sham-operated rats but not in AD rats. Electrical stimulation of the afferent aortic depressor nerve enhanced extracellular GABA and taurine in the posterior hypothalamic nucleus. The release rate of arginine was not influenced by alterations in baroreceptor activity either in sham-operated or in AD rats. The findings support the idea that, in the hypothalamus, GABA and taurine are involved in central blood pressure regulation. The release of these two amino acids seems to be driven tonically by baroreceptor impulses. Moreover, the findings indicate that the baroreceptors of the aortic arch play a crucial role in the mediation of changes in hypothalamic GABA and taurine outflow so as to counteract blood pressure fluctuations.

Spasmogenic action of beta-lactam antibiotics on the gastrointestinal tract of experimental animals.

We have investigated the effects of beta-lactam antibiotics on isolated preparations of rat fundus, ileum, and the body of feline stomach. Isotonic changes of isolated preparations were recorded. Benzylpenicillin (EC50 = 1.31 +/- 0.13 x 10(-5) M), ampicillin (EC50 = 2.16 +/- 0.15 x 10(-5) M), cefotaxime (EC50 = 1.33 +/- 0.15 x 10(-5) M), ceftriaxone (EC50 = 4.39 +/- 0.13 x 10(-5) M) and ceftazidime (EC50 = 1.42 +/- 0.01 x 10(-3) M) produced concentration-dependent tonic contractions of rat fundus. Rat ileum and feline stomach did not respond on these substances. Lidocaine (2.3 x 10(-5) M) and physostigmine (1.0 x 10(-8) M) significantly potentiated contractions produced by benzylpenicillin. On the other hand, methysergide (1.4 x 10(-7) M) and atropine (9.6 x 10(-9) M) significantly blocked tonic contractions produced by benzylpenicillin. Effects of beta-lactam antibiotics on smooth muscle isolated preparations were tissue and species dependent, indicating selectivity of their action.