Behavioral dissociation of anterodorsal and posteroventral hippocampus by subseizure stimulation in mice

BALB/c mice were bilaterally implanted with bipolar electrodes either in anterodorsal (ADH) or posteroventral hippocampus (PVH) in order to compare the effects of postsession electrical stimulation on memory processes. For each experiment, 30 s after the end of the first session, the animals were stimulated during 80 s. For both hippocampal regions, the stimulation intensity was half of the afterdischarge threshold value. Control groups were naive, ADH and PVH implanted non-stimulated animals. Different appetitive and aversive tasks were used. Subseizure stimulation never created a deficit. Depending on the region of the hippocampus stimulated and on the learning task, a retention enhancement was eventually observed. These data are in agreement with the involvement of hippocampus in initial stages of memory consolidation. Further, the subseizure stimulation permitted a functional dissociation between the two hippocampal regions. Both regions seemed involved in the integration of information, but the anterodorsal part would be rather related to behavioral inhibition, while the posteroventral part would have the capacity to induce an arousal state allowing behavioral flexibility.     

Comparative evaluation of the treatment of Sj?gren's syndrome with anti-rheumatic preparations

The paper is devoted to comparative assessment of combined therapy of prednisolone, chlorambucil, chloroquine phosphate and ibuprofen at small doses and its effect on clinicolaboratory signs of Sjogren's disease in 80 patients in the course of 1 and 5 years. Patients of the control group received only local therapy of the parotid glands. The results have demonstrated that combined therapy at small doses of prednisolone and chlorambucil (5 mg + 4 mg) is an effective method of treatment of the stomatological, ophthalmological and articular manifestations of SD and is also capable of preventing the systemic signs of disease. Combined therapy with chloroquine phosphate and ibuprofen neither influenced the clinicolaboratory signs of disease nor prevented disease progression with the development of systemic signs of diseases of various degrees. Disease progression was observed in 80% of patients receiving no basic drugs or receiving chloroquine phosphate+ibuprofen while in groups of patients receiving small doses of prednisolone and chloambucil disease progression was observed in 20% only.     

Pharmacokinetics of famotidine in patients with cirrhosis and ascites

Summary The pharmacokinetics of famotidine has been investigated in ascitic cirrhotic patients. 10 decompensated cirrhotic patients were studied (9 m, 1 f), who had normal renal function, and six healthy control subjects (4 m, 2 f), matched for age, sex and weight. Each subject received on two occasions, at least four days apart, a single oral (40 mg) or intravenous dose (20 mg) of famotidine, at 21.00 h in a randomised manner. Serial blood samples were collected and famotidine in plasma was determined by a HPLC/UV method. Plasma data were subjected to non compartmental pharmacokinetic analysis.There were no statistically significant differences in pharmacokinetic parameters between the two groups after either the intravenous or oral administration of famotidine.The findings suggest that the dose of famotidine may not require any adjustment in ascitic patients without renal failure.     

In vitro metabolism of ferroquine (SSR97193) in animal and human hepatic models and antimalarial activity of major metabolites on Plasmodium falciparum.

Ferroquine (SSR97193) has been shown to be a promising antimalarial, both on laboratory clones and on field isolates. So far, no resistance was documented in Plasmodium falciparum. In the present work, the metabolic pathway of ferroquine, based on experiments using animal and human hepatic models, is proposed. Ferroquine is metabolized mainly via an oxidative pathway into the major metabolite mono-N-demethyl ferroquine and then into di-N,N-demethyl ferroquine. Some other minor metabolic pathways were also identified. Cytochrome P450 isoforms 2C9, 2C19, and 3A4 and, possibly in some patients, isoform 2D6, are mainly involved in ferroquine oxidation. The metabolites were synthesized and tested against the 3D7 (chloroquine-sensitive) and W2 (chloroquine-resistant) P. falciparum strains. According to the results, the activity of the two main metabolites decreased compared with that of ferroquine; however, the activity of the mono-N-demethyl derivative is significantly higher than that of chloroquine on both strains, and the di-N-demethyl derivative remains more active than chloroquine on the chloroquine-resistant strain. These results further support the potential use of ferroquine against human malaria.     

Growth hormone releasing activity by intranasal administration of a synthetic hexapeptide (hexarelin)

OBJECTIVE Hexarelin is a new synthetic growth hormone releasing peptide. We have tested the efficacy of intranasal (i.n.) administration of hexarelin to stimulate plasma GH and have compared this to the intravenous (i.v.) administration of the peptide. PATIENTS Ten children with familial short stature (FSS) aged 5·5-15·5 years and two known GH deficient patients aged 24 and 28 years without GH treatment. METHODS All 12 subjects were submitted to i.v. (1 μg/kg) and i.n. (20 μg/kg) hexarelin tests with a one-week interval between tests. Blood samples for GH, TSH, fT4 and T3 were obtained at 0, 15, 30, 60, 90 and 120 minutes. The hormone determinations were made by standard radio-immunoassays (RIA). RESULTS Both the i.n. and i.v. administration of hexarelin induced a large GH response, the mean (±SD) being 72·2± 35·5 mU/l for the i.n. test and 79·6 ± 53·0 mU/l for the i.v. test. The peak GH in the i.v. test occurred at 15–30 minutes and in the i.n. test between 30 and 60 minutes. The GH deficient patients showed no GH response In either test. Plasma TSH decreased in the FSS children from a mean (±SD) of 1.0 ± 0·26 to 0·64±0 2 mU/l (P<0 005) during the i.n. test and from 1·0±0·3 to 0·7±0·3mU/l (P> 0 05) during the I.v. test. In the isolated GH deficient patient, plasma TSH decreased from 1·06±0·38 mU/l to 0·86±0·17 during the i.v. test and from 1·60±0·01 to 1·11±0·06mU/l during the i.n. test. There were no significant changes in plasma fT4 or T3 in any of the tests. CONCLUSIONS The synthetic hexapeptide hexarelin is a potent pituitary GH stimulator when administered intra-nasally. The GH response was similar to that observed after intravenous hexarelin. Simultaneously, there was a significant decrease in plasma TSH but the concentrations remained in the normal range. These findings appear to be of theoretical and practical relevance to the investigation and management of short children.     

Effectiveness of gentamicin-impregnated cement in the prevention of deep wound infection after primary total knee arthroplasty.

Effectiveness of gentamicin-impregnated cement in preventing deep wound infection after total knee arthroplasty (TKA) was estimated using data from prospective surveillance. In multivariate analysis, the protective effect of gentamicin-impregnated cement on the development of infection was close to the limit of significance. Gentamicin-impregnated cement may prevent TKA infections.     

Brain protection at the blood-cerebrospinal fluid interface involves a glutathione-dependent metabolic barrier mechanism.

The choroid plexuses (CPs) form a protective interface between the blood and the ventricular cerebrospinal fluid (CSF). To probe into the pathways by which CPs provide brain protection, we sought to evaluate the efficiency of glutathione conjugation in this barrier as a mechanism to prevent the entry of blood-borne electrophilic, potentially toxic compounds into the CSF, and we investigated the fate of the resulting metabolites. Rat CPs, as well as human CPs from both fetal and adult brains, displayed high glutathione-S-transferase activities. Using an in vitro model of the blood-CSF barrier consisting of choroidal epithelial cells cultured in a two-chambered device, we showed that glutathione conjugation can efficiently prevent the entry of 1-chloro-2,4-dinitrobenzene (CDNB) into the CSF, a model for electrophilic compounds. The duration of this enzymatic protection was set by the concentration of CDNB to which the epithelium was exposed, and this barrier effect was impaired only on severe epithelial intracellular glutathione and cysteine depletion. The conjugate was excreted from the choroidal cells in a polarized manner, mostly at the blood-facing membrane, via a high-capacity transport process, which is not a rate-limiting step in this detoxification pathway, and which may involve transporters of the ATP-binding cassette c(Abcc) and/or solute carrier 21 (Slc21) families. Supplying the choroidal epithelium at the blood-facing membrane with a therapeutically relevant concentration of N-acetylcysteine sustained this neuroprotective effect. Thus, glutathione conjugation at the CP epithelium coupled with the basolateral efflux of the resulting metabolites form an efficient blood-CSF enzymatic barrier, which can be enhanced by pharmacologically increasing glutathione synthesis within the epithelial cells.     

Effect of intervention to improve breastfeeding technique on the frequency of exclusive breastfeeding and lactation-related problems.

This randomized clinical trial compared frequencies of exclusive breastfeeding and lactation-related problems during the first 30 days among 74 mothers who received a 30-minute counseling session on breastfeeding technique in the maternity ward, and 137 controls. The frequency of exclusive breastfeeding among mothers who had received intervention was similar to controls by 7 days (79.7% vs 82.5%, respectively) and 30 days (60.8% vs 53.3%). There was no difference between groups in the frequency of sore nipples at 7 and 30 days, in breast engorgement and mastitis, and in the quality of breastfeeding technique at 30 days. Therefore, a single intervention at maternity was not sufficient to improve breastfeeding technique, increase exclusive breastfeeding rates, and reduce the incidence of breastfeeding problems during the first month.     

Use of stereotactic PET images in dosimetry planning of radiosurgery for brain tumors: clinical experience and proposed classification.

We developed a technique that allows the routine integration of PET in stereotactic neurosurgery, including radiosurgery. We report our clinical experience with the combined use of metabolic (i.e., PET) and anatomic (i.e., MRI and CT) images for the radiosurgical treatment of brain tumors. We propose a classification describing the relative role of the information provided by PET in this multimodality image-guided approach. METHODS: Between December 1999 and March 2003, 57 patients had stereotactic PET as part of their image acquisition for the planning of gamma knife radiosurgery. Together with stereotactic MRI and CT, stereotactic PET images were acquired on the same day using either (18)F-FDG or (11)C-methionine. PET images were imported in the planning software for the radiosurgery dosimetry, and the target volume was defined using the combined information of PET and MRI or CT. To analyze the specific contribution of the PET findings, we propose a classification that reflects the strategy used to define the target volume. RESULTS: The patients were offered radiosurgery with PET guidance when their tumor was ill-defined and we anticipated some limitation of target definition on MRI alone. This represents 10% of the radiosurgery procedures performed in our center during the same period of time. There were 40 primary brain lesions, 7 metastases, and 10 pituitary adenomas. Abnormal PET uptake was found in 62 of 72 targets (86%), and this information altered significantly the MRI-defined tumor in 43 targets (69%). CONCLUSION: The integration of PET in radiosurgery provides additional information that opens new perspectives for the optimization of the treatment of brain tumors.