Efficacy of probiotic Enterococcus faecium in combination with diclazuril against coccidiosis in experimentally infected broilers.

AIMS: The study was conducted to investigate the combination of a probiotic strain of Enterococcus faecium and diclazuril to control coccidiosis in broilers. METHODS AND RESULTS: A total of 240 one-day-old female broiler chicks were divided into eight groups (30 chicks per group): prophylactic groups (G1, G2 and G3) and therapeutic groups (G4, G5 and G6) and two control groups (untreated infected, G7 and untreated uninfected, G8 controls). In the prophylactic approach, diclazuril alone (G1), probiotic alone (G2) or a mixture of both probiotic and diclazuril (G3) was orally administered to the chicks via drinking water 10 days prior to the infection. However, in the therapeutic approach, G4, G5 and G6 birds were administered diclazuril alone, probiotic alone and diclazuril+probiotic mix, respectively, in drinking water for five consecutive days after the appearance of clinical signs of coccidiosis. Birds of both approaches and G7 were experimentally infected with 25 × 103 Eimeria-sporulated oocysts. Chicks in G3 showed the highest weight gain, the lowest lesion score, a low oocyst count and mortality rate among the challenged groups. Moderate lesion scores and oocyst counts were observed in chickens administered probiotics prophylactically. In the therapeutic approach, broilers in G6 but not G5 displayed a decreased mortality rate and lesion score in comparison to those in G7 and G8. However, the result of the probiotic-treated group was not significantly different from that in the untreated infected control group. CONCLUSION: The probiotic supplementation as a prophylactic approach can decrease the adverse effects of eimerian infection. In addition, the probiotic and diclazuril mix achieved a considerable improvement in the growth performance. Therefore, probiotic plus diclazuril combination achieved a synergistic effect. SIGNIFICANCE AND IMPACT OF THE STUDY: Investigation into the synergism/antagonism between a probiotic and diclazuril as anticoccidial agent and the difference in the timing of administration.

Microdialysis-directed Intra-tumor Pharmacokinetic Modeling of Methotrexate in Mice and Humans.

PURPOSE: To develop a quantitative pharmacokinetic model to characterize the disposition of methotrexate (MTX) at tumor site in tumor-bearing mice and to predict MTX concentrations in the human tumor. METHODS: The plasma profiles of MTX were obtained from normal mice, while microdialysis technique was employed to characterize the time course of MTX in tumor from breast tumor-bearing mice. Disposition profiles of plasma and tumor were analyzed by a hybrid physiologically-based pharmacokinetic (hPBPK) model that incorporates physiologically-relevant parameters such as tumor blood flow and volume, while plasma concentrations were used as a forcing input into the vascular-interstitial spaces of the tumor. The plasma profiles were initially described by a biexponential decay model to obtain a forcing function that enters into the vascular-interstitial spaces in the tumor. Using a defined forcing function, the tumor free concentrations were fitted to the hPBPK model. Based on the model developed, sensitivity analysis was conducted with a perturbation of PK parameters to predict different scenarios of intratumoral MTX transport. The relevant physiological PK parameters from the mouse model were then scaled-up and utilized to simulate human tumor concentrations. RESULTS: The mouse hPBPK model adequately characterized the concentration-time profiles of MTX in both plasma and tumor and produced various transfer rate constants between plasma and tumor. Our model was also able to reasonably predict MTX concentrations in the human tumor when human physiological data were utilized. CONCLUSIONS: The hPBPK model was able to quantitatively characterize the atypical transport of MTX in the tumor, supporting the idea that microdialysis is a valuable tool to study tumor biodistribution of drugs and to predict tumor concentrations in humans based on the pre-clinical data. This information can ultimately aid in the development of anticancer drugs with improved PK profiles. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Incorporating valsartan in sesame oil enriched self-nanoemulsifying system-loaded liquisolid tablets to improve its bioavailability.

Valsartan (VST) is a poorly soluble antihypertensive drug characterized by its limited dissolution rate and low bioavailability. This study aims to improve VST solubility and dissolution rate via developing liquisolid tablets (LSTs) containing a self-nanoemulsifying drug delivery system (SNEDDS), which is expected to enhance VST bioavailability. This aim was achieved via two designs of experiment. The first was the simplex-lattice design to optimize VST-loaded-SNEDDS using sesame oil, Tween 80, and polyethylene glycol 400. The second was the 32-3-level factorial design to optimize the liquisolid system using the SNEDDS-loaded VST and Neusilin®US2 as a carrier and fumed silica as a coating material. Different excipient ratios (X1) and varioussuper-disintegrants (X2) were also used in developing the optimized VST-LSTs. Thein vitrodissolution of VST from LSTs was compared with the marketed product (Diovan®). Non-compartmental analysis of plasma data after extravascular input with the linear trapezoidal method was used to calculate thepharmacokinetic parameters of the optimized VST-LSTs compared with the marketed tablet in male Wistar rats. The optimized SNEDDS compromised 24.9% sesame oil, 33.3% surfactant, and 41.8% cosurfactant, giving 173.9 nm size and 63.9 mg/ml loading capacity. Also, the SNEDDS-loaded VST tablet revealed good quality attributes with the release of 75% of its content in 5 min and 100% within 15 min. On the other hand, the marketed product took 1 h for the entire drug to be released.Moreover, the maximum plasma concentration (Cmax) of the optimizedVST-LSTwas6585.33 ng/ml within 1 h (Tmax), compared to 2884.67 ng/ml within 2 h of the marketed tablet.The relative bioavailability of the SNEDDS-loaded VST tablet was 213.7% compared to that of the marketed tablet, indicating that this formulation approach could be applied for increasing solubility, dissolution behavior in GIT, and bioavailability of poorly water-soluble drugs.

The Encapsulation of Febuxostat into Emulsomes Strongly Enhances the Cytotoxic Potential of the Drug on HCT 116 Colon Cancer Cells.

Febuxostat (FBX) is a drug able to inhibit xanthine oxidase and reduce uric acid production commonly used for the treatment of hyperuricemia in subjects suffering from gout. Several studies have also been directed at its use as anti-cancer drug during the last years, opening a window for its off-label use. In the present study, an optimized formulation in terms of vesicle size and drug release, obtained by encapsulation of FBX into the emulsomes (FBX-EMLs), was evaluated for its cytotoxic potential in human colorectal carcinoma (HCT 116) cells. The optimized FBX-EMLs formula had an improved half maximal inhibitory concentration (IC50), about 4-fold lower, compared to the free drug. The cell cycle analysis showed a significant inhibition of the HCT 116 cells proliferation following FBX-EMLs treatment compared to all the other conditions, with a higher number of cells accumulating on G2/M and pre-G1 phases, paralleled by a significant reduction of cells in G0/G1 and S phases. The optimized formula was also able to significantly increase the percentage of cell population in both early and late stages of apoptosis, characterized by a higher intracellular caspase-3 concentration, as well as percentage of necrotic cells. Lastly, the FBX ability to decrease the mitochondrial membrane potential was enhanced when the drug was delivered into the EMLs. In conclusion, the new formulation of FBX into EMLs improved all the parameters related to the anti-proliferative activity and the toxic potential of the drug towards colorectal cancer cells.

Transtemporal-transchoroidal approach and its transamygdala extension to the posterior chiasmatic cistern and diencephalo-mesencephalic lesions.

The aim of this report is to illustrate the successful surgical management of five patients with suprasellar retrochiasmatic and diencephalo-mesencephalic tumours, using a trans-amygdala extension of the trans-temporal/trans-choroidal fissure approach. The procedure is described for five surgically treated patients with such lesions that includes three retrochiasmatic craniopharyngiomas, one hypothalamic hamartoma, and one pilocytic astrocytoma in the left crus cerebri. The management procedure included computed tomography scan (CT scan) and magnetic resonance imaging (MRI). The trans-temporal/trans-choroidal fissure approach enabled us to perform total tumour resection in four patients and a subtotal resection in one. Some technical aspects and pitfalls of the procedure are discussed. This method creates optimum conditions for a radical excision of various suprasellar retrochiasmatic and diencephalo-mesencephalic tumours without mortality and only minimum morbidity. However, no single surgical approach can provide access to the entire variety of tumours located in the suprasellar retrochiasmatic and diencephalo-mesencepalic region. Surgical approaches must be tailored to the site, type of lesion, and its extensions. This method is only another surgical option. Its successful use requires a familiarity with the anatomy of these regions and an understanding of its specificity for a radical excision of some selected tumours, as well as its limitations to access others types of lesions. Although, it seems effective, this approach needs to be evaluated by further experience, owing to the small number of patients reported in this series.

Trends in HIV infection among sexually transmitted disease patients in Paris.

OBJECTIVE: To assess trends in HIV infection among sexually transmitted disease (STD) patients. DESIGN: Repeated unlinked anonymous survey, 1991-1993. SETTING: STD clinics in Paris, France. SUBJECTS: Patients (n = 4354) with a new suspected STD. METHODS: HIV antibody testing, using blood from syphilis samples. RESULTS: HIV prevalences were stable over time in all transmission groups. One-third of homo-/bisexual men were HIV-positive. Prevalence was 2.5 times higher among heterosexual patients from Africa or the Caribbean than among those from other countries. Among patients under 25 years of age prevalence significantly decreased from 4.3% in 1991 to 0.8% in 1993 (P = 0.01). Among homo-/bisexual men, despite a 50% reduction in the incidence of STD, the absolute number of those newly HIV-infected remained stable; median age increased from 28 years in 1991 to 32 years in 1993 (P = 0.02). Among heterosexuals, trends in HIV incidence were difficult to assess: recently infected patients were more likely to be identified in 1993 than in 1991, since the proportion of patients who reported a recent HIV-negative test increased over time. CONCLUSION: Prevalence studies contribute to define specific subgroups which should be targeted for prevention (HIV-positive or older homosexuals, heterosexuals from Africa and the Caribbean). Despite a decrease in both overall STD incidence and HIV prevalence among patients aged under 25 years, overall HIV incidence has not decreased, at least among homo-/bisexual men in whom recent HIV infections occurred at a high rate overall, and increased in those aged 35 years or more. Sentinel site-based HIV seroprevalence studies are best interpreted in the light of results obtained from different populations and through routine surveillance of STD.

HIV prevalence and risk behaviour among intravenous drug users attending HIV counselling and testing centres in Paris.

This study was designed to analyse sexual and drug use behaviour, to determine whether increased awareness can lead to behaviour change, and to evaluate the association between HIV seropositivity and potential risk factors. A 4-month survey was carried out on 147 IVDUs attending three HIV counselling and testing centres, 98% of whom had been using heroin for an average of 7 years, 85% in association with other drugs. Two-thirds of injectors reported having used "safer" injecting practices in the previous year. Most of the IVDUs were heterosexual, and had had an average of three sexual partners in the previous year. More than half of them had had high risk partners. Condoms were used by only 25% of IVDUs, and were more likely to be used with seropositive partners (38% versus 12.7%, p = 0.02). Patients considering themselves to be well informed about HIV transmission shared syringes significantly less often, but had the same sexual behaviour patterns as other subjects. The HIV prevalence rate (8.2%) in our sample was not statistically related to any risk factor apart from drug use duration, the latter possibly reflecting a cumulative exposure to HIV risks. Since sexual risk appears to be a potential long-term hazard for IVDUs, it is important that more attention be paid to providing counselling to specifically address this issue.

Acute presentation of hydromyelia in a child.

The authors document a rapid development, within 3 weeks, of hydromyelia in a 12 year-old boy. The boy was admitted to a local hospital because of drowsiness and persistent severe neck pain. Neurological examination disclosed a lethargic boy with no neurological deficit other than Parinaud's sign. During his transfer to our department, he presented a cardio-respiratory arrest with coma and bilateral mydriasis. External ventricular drain and craniocervical decompression achieved excellent clinical and neuroradiological outcomes. The development of hydromyelia in this case is caused by obstruction to the natural cerebrospinal fluid pathway at the craniocervical junction and the cardio-respiratory arrest is provoked by a brain stem compression against the clivus and odontoid process. This report illustrates that hydromyelia may complicate acute obstructive hydrocephalus due to acquired Chiari malformation.

Interaction between Light Intensity and NaCl Salinity and Their Effects on Growth, CO(2) Assimilation, and Photosynthate Conversion in Young Broad Beans.

Seedings of Vicia faba were grown for four weeks at two different light intensities (55 and 105 watts per square meter) in a saline (50 millimolar NaCl) and nonsaline nutrient solution. NaCl salinity depressed growth and restricted protein formation, CO(2) assimilation, and especially the incorporation of photosynthates into the lipid fraction. Conversion of photosynthates in leaves was much more affected by salinity than was photosynthate turnover in roots. The detrimental effect of NaCl salinity on growth, protein formation, and CO(2) assimilation was greater under low than under high light conditions. Plants of the high light intensity treatment were more capable of excluding Na(+) and Cl(-) and accumulating nutrient cation species (Ca(2+), K(+), Mg(2+)) than plants grown under low light intensity. It is suggested that the improved ionic status provided better conditions for protein synthesis, CO(2) assimilation, and especially for the conversion of photosynthates into lipids.

[Natural infestation of Phlebotomus papatasi in a focus of zoonotic cutaneous leishmaniasis in Tunisia]. / Infestation naturelle de Phlebotomus papatasi dans un foyer de leishmaniose cutanée zoonotique en Tunisie.

The presence of Phlebotomus papatasi naturally infected with Leishmania (2 females out of 24), is reported for the first time, in a Tunisian zoonotic cutaneous leishmaniasis focus.

Demographic and behavioral predictors of knowledge and HIV seropositivity: results of a survey conducted in three anonymous and free counselling and testing centers.

This paper deals with subjects seeking counselling and testing for human immunodeficiency virus (HIV); it analyses which sociodemographic and behavioral characteristics are related to beliefs concerning HIV infection and to HIV seropositivity. A one month survey among individuals who attended HIV testing in three anonymous and free centers (CIDAGs) was carried out in Paris city, on March 1994. 2059 subjects completed a self-administered questionnaire. Data collected included demographic information, sexual and IVDU behavior, and HIV seropositivity. Subjects also had to evaluate their own risk of getting the acquired immunodeficiency syndrome (AIDS) and the perceived risk of getting AIDS in specific situations such as unprotected anal/vaginal intercourse with a casual partner, with multiple partners, with a seropositive partner, current dental treatment, French kiss, etc.... Multiple linear and logistic regressions have been used to model the dependent variables. Subjects correctly evaluated the risk level of HIV transmission associated with different situations, and women, young men and those engaged in homo/bisexual behavior were in general more conscious of the increased danger resulting from high risk sexual practices. Among males, homo/bisexuals, drug users and the less educated considered themselves to be more at risk. The most important factors related to HIV seropositivity were sexual orientation, intravenous drug use (IVDU), and the perceived risk of getting aids. Despite a good awareness of HIV contamination and an accurate perception of their own risk, many subjects continued to engage in high risk AIDS activities. Better targeted interventions need to be developed to promote and maintain behavior changes.

[An entomological survey in the focus of zoonotic cutaneous leishmaniasis (Leishmania major) of Sidi Bouzid (Tunisia) in 1985]. / Enquête entomologique dans le foyer de leishmaniose cutanée zoonotique (Leishmania major) de Sidi Bouzid (Tunisie) en 1985.

An entomological survey carried out in 1985 in the zoonotic cutaneous leishmaniasis foci of the Center of Tunisia (Sidi Bouzid Governorate), showed the presence of 7 phlebotomine species. Phlebotomus (P) papatasi, the most abundant species (84.6%), was essentially trapped in rodent burrows. Its anthropophily was demonstrated by man-baiting catch. The highest population density was observed during July and August, for P. papatasi. Its role in the transmission of Z. C. L. in Tunisia is discussed. P. perniciosus, less abundant (13.2%) was mostly trapped in animal resting places. Only few specimens of P. longieuspis, P. perfiliewi, Sergentomyia (S) minuta, S. antennata and S. dreyfussi were observed.