Norfloxacin exhibits negligible serum concentrations after repeated conjunctival instillation in children.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to F Drago.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Male rats of the Wistar strain were selected as good copulators (displaying at least 1 ejaculation in each of three consecutive tests for male sexual behavior) and sexually sluggish animals (displaying no ejaculations in each of three consecutive tests). The administration of low doses (1 and 2.5 mg/kg, i.p.) of kainic acid in sexually sluggish rats induced an enhancement of some parameters of copulatory behavior. In particular, significant reductions in latency to the first mount and intromission and increases in frequency of mounts and intromissions were observed. In contrast, the drug failed to exert any effect in good copulators. At the dose of 5 mg/kg (i.p.) kainic acid exerted an inhibitory effect on sexual behavior parameters both in good copulators and in sluggish rats. A persistent increase in latency to the first mount, intromission and ejaculation, and reduction in frequency of mounts, intromissions and ejaculation both in good copulators and in sluggish rats were observed 20 days after kainic acid treatment at the higher dose. No persistent effect of kainic acid 1 and 2.5 mg/kg was observed 20 days after treatment. These results suggest that kainic acid may affect in a dose-dependent manner several copulatory parameters of male sexual behavior repertoire. The bimodal effects could be explained considering a possible interaction of kainic acid with different neurotransmissions or receptor subtypes.
The sexual dimorphism of gastroduodenal ulceration is suggested on the basis of clinical and experimental observations. This difference probably relates to the actions of endogenous sexual steroids. In the present study, the role of testosterone was evaluated in the generation of gastroduodenal mucosal injury provoked by cysteamine (400 mg/kg, s.c.). We found that macroscopic mucosal damage and microvascular (125)I-human serum albumin leakage (2 microCi/kg, i.v.) developed in the stomach and duodenum of male rats 24 h after the administration of cysteamine. This mucosal injury was prevented by orchidectomy and by the pretreatment with the antiandrogen, cyproterone acetate (12 mg/kg per day for 8 consecutive days). It was also shown that pretreatment with testosterone (4-20 mg/kg per week) dose-dependently aggravated cysteamine-induced gastroduodenal mucosal injury. Our results thus suggest an aggressive role of testosterone in the generation of cysteamine-induced gastroduodenal ulceration.
Explore the source record for details and available documents.
A number of experiments were carried out to explore the behavioral profile of a novel antipsychotic, risperidone, after acute or chronic administration, in a dose range of 0.1-10 mg kg-1. This drug did not affect the acquisition and retention of avoidance behaviors in a dose of 0.1 mg kg-1, either after acute or chronic administration. Higher doses induced a inhibited acquisition and a facilitated extinction (only after chronic treatment) of active avoidance behavior, but no significant effect on the retention of passive avoidance responses. In contrast, haloperidol inhibited the acquisition and facilitated the extinction of active avoidance behavior, and reduced the retention of passive avoidance reaction at the dose of 0.1 mg kg-1 injected either acutely or chronically. Ambulation and rearing of rats rated in an open field was increased by risperidone injected acutely at the dose of 1 mg kg-1. Under the same experimental conditions, grooming appeared to be reduced. In the same test, acute or chronic haloperidol 1 or 10 mg kg-1 inhibited all behavioral items. Furthermore, in contrast to haloperidol, the acute or chronic administration of risperidone in a dose range of 0.1-10 mg kg-1 did not substantially induce catalepsy and did not affect apomorphine-induced stereotypies. Also, the dose of 0.1 mg kg-1 induced a facilitation of male sexual behavior by increasing the frequency and reducing the latency of mountings, intromissions and ejaculations, while haloperidol 1 or 10 mg kg-1 inhibited this behavior. These findings suggest that the pharmacological profile of risperidone differs from that of classical neuroleptics, like haloperidol, probably due to different mechanism or site of action.
The effect of 7-days BID (twice in a day) or TID (three times in a day) administration of the eye-drop combinations of timolol and pilocarpine (0.5% and 2%, respectively), metipranolol and pilocarpine (0.1% and 2%, respectively) or placebo on intraocular pressure (IOP) and heart rate (HR) of conscious rabbits were studied in order to assess the pharmacological potency of the combinations and their heart side effects. TID administration of both pharmacological combinations was followed by similar decrease of IOP as measured over 24 h (at 4.00 and 20.00 h). After the BID administration, a reduction in IOP was observed only twice with the timolol-pilocarpine combination. In contrast, a constant reduction in IOP was seen with the metipranolol-pilocarpine combination. Furthermore, the TID administration of the timolol-pilocarpine combination exerted a decrease of IOP that appeared to be more pronounced than that observed after the BID administration of the same combination, while no difference was found between the TID and BID administration of the metipranolol-pilocarpine treatment. Heart rate, when measured after 7 days of treatment, appeared to be constantly decreased only in the group of animals which received the TID administration of timolol-pilocarpine combination. The present results suggest that the BID or TID administration of metipranolol-pilocarpine combination was fully effective in reducing IOP without influencing HR. The timolol-pilocarpine association appeared to be fully active in reducing IOP only under the TID administration schedule. However, this rate of administration was followed by a constant reduction of HR. Thus, on a dose basis the metipranolol-pilocarpine combination appeared to be more effective in reducing IOP and less effective in inducing bradycardia than the timolol-pilocarpine association.
Nicergoline is an ergot alkaloid derivative acting as a neuroprotective agent. In the present investigation, b-wave time-course recovery profiles under both light- and dark-adapted conditions, were studied in order to evaluate the possible effectiveness of nicergoline in the protection of the rabbit retina. Retinal ischaemia was induced by bilateral occlusion of common carotid artery in male rabbit of the Dutch strain. Groups of animals were subjected to 15-, 30- and 60-min periods of ischaemia under pentobarbital anaesthesia. Electroretinogram recordings were simultaneously obtained from both eyes, using, as the stimulus, the brightest flash from a stimulator positioned 15 cm in front of each eye. The treatment with nicergoline, administered immediately before the carotid occlusion, induced a significant protection only when the ischaemia seemed to cause retinal damage that the reperfusion alone was not able to recover completely. Nicergoline did not modify the recovery rate after 15-min or 30-min light-adapted and 15-min dark-adapted ischaemia; in these conditions the controls showed a full recovery. After 30-min dark-adapted ischaemia, the maximum recovery of the controls was 82%, and nicergoline significantly improved b-wave amplitude at all time points of reperfusion up to the complete recovery. Rabbit retina was irreversibly damaged by a 60-min ischaemia. In these conditions nicergoline significantly increased the percentage of b-wave recovery both in light- and dark-adapted ERG. Nicergoline, probably on the basis of its metabolic actions, seems to be effective in severe conditions of hypoxia and is more potent in dark than in light-adapted conditions. Its effectiveness in these experimental conditions could be justified by the different oxygen consumption of the photoreceptors in light and dark and the different sensitivity of cones and rods to the ischaemia.
The effect of repeated morphine administration on conditioned place preference (CPP) using a novel treatment schedule, i.e., drug treatment was always contingent with the conditioned environmental stimuli, was investigated. We also examined whether changes in the mu- and kappa-opioid receptor binding occurred in the brain of morphine-treated animals. Intraperitoneal (i.p.) administration of morphine (2 and 10 mg/kg) induced a place preference after 8 daily conditioning trials (4 morphine injections on alternate trials), the level of preference being the same with the two doses of the opiate. No change in place preference was observed in the morphine-treated rats at 2 mg/kg, when animals were further trained up to a total of 32 conditioning trials (16 morphine injections). Conversely, after 20 conditioning trials (10 morphine injections), a stronger CPP response developed in the morphine-treated rats at 10 mg/kg. Signs of morphine withdrawal were never detected in morphine-treated rats during the experiment. Loss of body weight (index of opiate dependence) was not observed either 24 h or 48 h after the last morphine administration. mu- and kappa-opioid receptor density and affinity were not affected by repeated morphine administrations at either dose. The results demonstrate that no tolerance develops to the rewarding properties of morphine. Indeed, a sensitisation effect may occur at increasing doses of the opiate. Furthermore, changes in the rewarding effect of morphine are not dependent upon alterations in opioid receptors involved in the reinforcing mechanisms.
It is known that cysteamine ulcerogenic effect depends, among others, on a depletion of somatostatin in the gastro-intestinal tract. Since growth hormone (GH) causes the release of hypothalamic somatostatin (SRIH) and potentiates the ulcerogenic action of cysteamine we have studied the influence of GH on gastro-duodenal mucosa levels of SRIH, and its relevance for the ulcerogenic action of cysteamine. Female rats of the Sprague-Dawley strain were pretreated with GH (0.25, 0.5 or 1 mg/kg) and subjected to cysteamine-induced gastric lesions. These animals showed an increased mortality and severity of gastric lesions. The measurement of gastric and duodenal barrier mucus levels revealed that GH administration was followed by a decrease in mucus production. Pretreatment with SRIH (25 or 50 microg/kg) was followed by a decreased percent incidence and severity of gastric mucosa lesions induced by cysteamine. The mucus production was increased by SRIH administration. GH pretreatment was followed by a reduction of SRIH-like immunoreactivity in gastro-duodenal mucosa and an increase of insulin plasma levels. Acute injection of cysteamine per se was also followed by a decrease of gastro-duodenal SRIH and an increase in insulin plasma levels. These results suggest that high levels of plasma GH, as induced by exogenous GH administration, may cause a decrease of SRIH gastro-intestinal content and this in turn may potentiate the ulcerogenic activity of cysteamine.
The role of central vasopressin V1 receptors in grooming behavior induced by vasopressin and oxytocin was studied in male rats of the Wistar strain. The intracerebroventricular (ICV) injection of vasopressin (3 micrograms/5 microliters) induced hypothermia and enhanced novelty-induced grooming behavior. Enhanced grooming but not hypothermia was also induced by ICV injection of oxytocin (3 micrograms/5 microliters). The central administration of a selective vasopressin V1 receptor antagonist prevented the stimulating action of vasopressin on novelty-induced grooming and its hypothermic effect. The ICV injection of a selective vasopressin V2 receptor antagonist failed to affect vasopressin-induced grooming and hypothermic effect. An increase in core temperature was observed in oxytocin-injected animals pretreated with the vasopressin V1 receptor antagonist. Furthermore, pretreatment with the antagonist did not affect grooming induced by oxytocin. These results suggest that enhancement of grooming behavior and influence on thermoregulation are differently regulated by central receptors for vasopressin and oxytocin.
After mating with a sexually active male, groups of female Sprague-Dawley rats were injected with cysteamine (400 mg/kg, subcutaneously) at day 0 (controls), day 5 (early-stage pregnancy), and day 18 (late-stage pregnancy) of pregnancy. In contrast to late-stage pregnancy rats, early-stage pregnancy animals showed a decrease of cysteamine-induced gastroduodenal lesions. When subjected to cysteamine injection, both nonpregnant female and male rats treated for eight days with progesterone (300 microg/rat, subcutaneously) showed a reduced incidence of gastroduodenal lesions. No effect was found in animals pretreated with 17beta-estradiol (200 microg/rat, subcutaneously). Furthermore, increased gastroduodenal mucus levels were found in early-stage pregnancy rats and in animals pretreated with progesterone. These results suggest that increased progesterone plasma levels during early-stage pregnancy may be involved in pregnancy-induced gastric and duodenal protection. This effect may be related to an increase in gastric and duodenal mucus production induced by this hormone.
Cimetidine and ranitine are histamine H2-receptor blockers widely used for the treatment of gastric hypersecretion and duodenal pathologies. They are known to induce hyperprolactinemia in humans. Forty-six patients treated with cimetidine or ranitidine who were exhibiting a neurobehavioral syndrome after withdrawal of the drugs were selected. This syndrome was associated with a drop in plasma prolactin levels. The symptoms of this syndrome were greatly improved by restoration of treatment with the same drugs and reappeared when the treatment was again suspended. This syndrome was inhibited in 36 patients by administration of domperidone (30 mg/day), a drug inducing hyperprolactinemia without crossing the blood-brain barrier, as compared with 10 control patients treated with placebo. These results suggest that the drop in prolactin levels occurring when cimetidine and ranitidine are suspended may contribute to the development of this syndrome. Also, the withdrawal of H2-receptor blockers could be included among the possible causes of some neurotic syndromes.
Explore the source record for details and available documents.
This study investigated the value of permanent atrial pacing as an adjunct to the current therapy in the chronic management of recurrent postoperative atrial reentrant tachycardia in patients with complex congenital heart disease. We studied the postpacing clinical course in 18 patients with recurrent atrial reentrant tachycardias unresponsive to conventional therapy who had an implanted atrial pacemaker. The pacemaker was programmed at a lower pacing rate 20% faster than the spontaneous mean daily rate previously determined with 24-hour Holter monitoring. Serial Holter recordings and pacemaker programming sessions were subsequently performed trying to maintain a paced atrial rhythm overdriving the spontaneous rhythm as long as possible. Twenty-four hour Holter monitoring documented a prevalent (> 80%) paced rhythm during the daily hours in all patients during the follow-up; all patients, however, required at least once a variation in programmed mode and pacing rate. Antiarrhythmic medications were discontinued after 6 months if the patient remained arrhythmia free while on pacing. Recurrences of atrial reentrant tachycardia occurred in five patients (29%) during the initial 6 months interval after the pacemaker implantation, while late recurrences occurred in only two patients (11%). One patient died suddenly 10 months after the pacemaker implant. At the end of the follow-up, 15 patients (83%) were arrhythmia-free and only 2 of them were still on antiarrhythmic drugs. We conclude that permanent atrial overdrive pacing can be an important tool in the management of patients with atrial reentrant tachycardia following repair of congenital heart disease.
BACKGROUND: Clinical evidence suggests a viral etiology for pityriasis rosea (PR). OBJECTIVE: To evaluate human herpesvirus (HHV)-6 and HHV-7 as candidates for the etiology of PR. METHODS: Blood and skin tissue from 12 patients with acute PR, and 12 patients with other dermatoses were studied, as well as blood samples from 25 healthy persons. Serum interferon (IFN)-alpha and IFN-gamma were analyzed by ELISA. Analysis of morphological changes in cocultured peripheral blood mononuclear cells (PBMC) and electron microscopy (EM) to identify viral particles were performed. Polymerase chain reaction (PCR) with specific primers for HHV-6 and HHV-7 DNA sequences was performed on the plasma and PBMC of patients and healthy controls and on the skin of patients with PR and other skin diseases. RESULTS: PR plasma contained detectable IFN-alpha and IFN-gamma, whereas plasma from controls did not. PBMC from PR patients showed ballooning cells and syncytia after 7 days in culture whereas PBMC from controls and recovered PR patients did not. This cytopathic effect was also documented in a PR patient who relapsed and in Sup-T1 cell cultures inoculated with the cell-free supernatant from centrifuged cultured PBMC; in this supernatant, herpesvirus, virions were detected by EM, PCR identified HHV-7 DNA in PBMC, plasma and skin from all patients with active PR and in the PBMC only of 5 patients tested 10-14 months later. Weaker signals of HHV-7 DNA were detected in PBMC of 11 controls, but not in their plasma. Skin was negative for HHV-7 in all control specimens. CONCLUSIONS: Although the detection of HHV-7 DNA in PBMC and tissues does not prove directly a causal role, HHV-7 DNA in cell-free plasma corresponds to active replication which supports a causal relationship. We propose that PR is a clinical presentation of HHV-7 reactivation.
Explore the source record for details and available documents.