Quantitative Phase-Contrast MR Angiography to Measure Hemodynamic Changes in Idiopathic Intracranial Hypertension.

BACKGROUND AND PURPOSE: Idiopathic intracranial hypertension is a syndrome of raised intracranial pressure of unknown etiology. Few MR imaging-based studies have investigated arterial and venous blood flow in these patients. Results are inconclusive, and to our knowledge, no comparison of the hemodynamic parameters before and after CSF pressure reduction has been published. The aim of this study was to assess the short-term effects of normalizing CSF pressure on intracranial flow to better understand the pathophysiology of idiopathic intracranial hypertension. MATERIALS AND METHODS: In this study, we performed quantitative MR imaging-derived flow measurements of brain-supplying arteries and draining veins/dural sinuses to visualize hemodynamic changes in patients with idiopathic intracranial hypertension before and after therapy by lumbar puncture in comparison with a healthy control group. RESULTS: We found differences in patients before and after lumbar puncture in the calculated resistance and pulsatility indices in the superior sagittal sinus. Venous pulsatility showed a negative correlation with CSF pressure in untreated patients. Additionally, there was a trend toward lower flow in the superior sagittal sinus in patients compared with healthy controls. Flow in the internal jugular veins was significantly reduced by lumbar puncture, and the resistance and pulsatility indices differed in patients and controls. The arterial flow was not influenced by pressure normalization. CONCLUSIONS: The results of the present study indicate that venous but not arterial blood flow differs in patients compared with controls and that calculating resistance and pulsatility indices may contribute to assessing short-term hemodynamic changes in patients with diagnosed idiopathic intracranial hypertension before and after CSF diversion.

Effect of genetic and nongenetic factors on chemical composition of individual milk samples from dromedary camels (Camelus dromedarius) under intensive management.

The aims of the present study were to monitor the changes in gross chemical composition of individual dromedary camel milk over a 5-yr period, to provide reference values, and to determine the effect of genetic and nongenetic factors influencing camel milk composition under intensive management. A total of 1,528 lactating dromedary camels were included in the study. Animals were fed a constant diet and were milked twice a day in a herringbone parlor. Milk samples were collected at monthly intervals using a sampling device and then fat, protein, lactose, total solids (TS), and solids-nonfat (SNF) concentrations of raw camel milk were determined with an automatic milk analyzer. For each milk sample, production parameters were recorded and quantities (grams) of milk constituents were calculated. The overall mean quantity and fat, protein, lactose, SNF, and TS concentrations of the morning milk were 4.0 kg, 2.58%, 2.95%, 4.19%, 8.08%, and 10.46%, respectively. Milk quantity showed a positive correlation with lactose and a negative correlation with all other components. Parity exerted a strong effect on all milk parameters. Primiparous dromedaries (n = 60) produced less milk with higher concentrations of components than did multiparous animals (n = 1,468). Milk composition varied among the 7 breeds tested, but none of the genotypes was found to be superior to the others in this respect. We detected a significant, yet small calf sex-biased difference in milk yield and composition. Stage of lactation and season strongly influenced milk yield and all milk components. We also found a significant interaction between month postpartum (mPP) and month of the year. The concentration of all milk components decreased from 1 to 5 mPP. Later, lactose concentration and quantity continued to decrease parallel with decreasing milk production. The concentration of other components showed a temporary increase in mid lactation, from 6 to 11 mPP, and in late lactation, from 18 to 23 mPP. Mean fat, protein, SNF, and TS concentrations showed a high seasonal variation (9.5 to 28.7%), with the lowest and highest values being measured during summer and winter, respectively. This seasonal variation was independent of nutrition and may reflect an endogenous circannual rhythm. We observed a noticeable variation among years. Dromedary camels could provide a useful in vivo model to study the homeorhetic regulation of mammary cell function by endogenous and environmental factors.

Effect of pregnancy and embryonic mortality on milk production in dromedary camels (Camelus dromedarius).

The main objective of the present study was to compare milk production in pregnant versus nonpregnant dromedary camels. In addition, we described the effect of embryonic mortality on lactation and measured serum progesterone levels until d 60 to 90 of gestation. Twenty-five multiparous camels were selected in midlactation for 2 studies in consecutive years. Camels were mated naturally when the size of the dominant follicle reached 1.2 to 1.5cm. Pregnancy was diagnosed by ultrasonography and progesterone determination. In the first experiment (Exp 1), 8 of 11 animals conceived at 284±21.5d postpartum. Three pregnant dromedaries were given PGF2α to induce luteolysis and pregnancy loss on d 62 and spontaneous embryonic loss was detected in 2 camels (on d 27 and 60). Animals were allotted to 3 groups retrospectively: nonpregnant camels (group 1, n=4), pregnant camels (group 2; n=3), and camels with embryonic loss after d 55 (group 3; n=4). In the second study (Exp 2), 14 dromedaries were mated during midlactation. Seven of them failed to conceive (group 1) and 7 became pregnant (group 2). No embryonic loss was detected in Exp 2. Turning points in milk production were identified by change point analysis. In nonpregnant dromedaries (group 1), milk decreased slowly over time without significant change point. In pregnant camels (group 2), a gradual decline until 4 wk after mating was followed by a sudden drop, and the change point model resulted in one breakpoint at d 28±7 and 35±3 of gestation in Exp 1 and Exp 2, respectively. In camels with embryonic mortality (group 3, Exp 1), milk yield started to decline similarly as in pregnant animals, but milk production increased gradually after embryonic loss and reached similar levels as in their nonpregnant herdmates. Change point analysis for group 3 resulted in 2 turning points at 30±4 and 48±4d after conception. Mean length of lactation was shorter by 230 (34.2%) and by 249d (37.6%) and mean total lactation production was decreased by 1,532 (31.6%) and 2,151 kg (44.3%) in pregnant compared with nonpregnant camels in Exp 1 and Exp 2, respectively. We concluded that the calving interval can be shortened by mating during midlactation. However, pregnancy has a strong negative effect on milk production as dromedaries stop lactating by the fourth month of gestation. Following embryonic mortality within 3mo of conception, milk production is restored.

Microbiological quality and somatic cell count in bulk milk of dromedary camels (Camelus dromedarius): descriptive statistics, correlations, and factors of variation.

The objectives of the present study were to monitor the microbiological quality and somatic cell count (SCC) of bulk tank milk at the world's first large-scale camel dairy farm for a 2-yr period, to compare the results of 2 methods for the enumeration of SCC, to evaluate correlation among milk quality indicators, and to determine the effect of specific factors (year, season, stage of lactation, and level of production) on milk quality indicators. The study was conducted from January 2008 to January 2010. Total viable count (TVC), coliform count (CC), California Mastitis Test (CMT) score, and SCC were determined from daily bulk milk samples. Somatic cell count was measured by using a direct microscopic method and with an automatic cell counter. In addition, production parameters [total daily milk production (TDM, kg), number of milking camels (NMC), average milk per camel (AMC, kg)] and stage of lactation (average postpartum days, PPD) were recorded for each test day. A strong correlation (r=0.33) was found between the 2 methods for SCC enumeration; however, values derived using the microscopic method were higher. The geometric means of SCC and TVC were 394×10(3) cells/mL and 5,157 cfu/mL during the observation period, respectively. Somatic cell count was >500×10(3) cells/mL on 14.6% (106/725) and TVC was >10×10(3) cfu/mL on 4.0% (30/742) of the test days. Both milk quality indicators had a distinct seasonal pattern. For log SCC, the mean was lowest in summer and highest in autumn. The seasonal pattern of log TVC was slightly different, with the lowest values being recorded during the spring. The monthly mean TVC pattern showed a clear difference between years. Coliform count was <10 cfu/mL in most of the samples (709/742, 95.6%). A positive correlation was found between log SCC and log TVC (r=0.32), between log SCC and CMT score (r=0.26), and between log TVC and CC in yr 1 (r=0.30). All production parameters and stage of lactation showed strong seasonal variation. Log SCC was negatively correlated with TDM (r=-0.35), AMC (r=-0.37), and NMC (r=-0.15) and positively correlated with PPD (r=0.40). Log TVC had a negative correlation with AMC (r=-0.40) but a positive correlation with NMC (r=0.32), TDM (r=0.16), and PPD (r=0.45). The linear mixed model with stepwise variable selection showed that the main sources of log SCC variation were PPD, TDM, PPD × season, and season. For log TVC, the same factors and year contributed to the variation.

Use of assisted reproduction for the improvement of milk production in dairy camels (Camelus dromedarius).

Despite their production potential and ability to survive on marginal resources in extreme conditions, dromedaries have not been exploited as an important food source. Camels have not been specifically selected for milk production, and genetic improvement has been negligible. High individual variation in milk production both within the population and within breeds provides a good base for selection and genetic progress. In this paper, we discuss the possibilities and constraints of selective breeding for milk production in camels, and include a summary of the use of embryo transfer at the world's first camel dairy farm. Embryo transfer is an integral part of the breeding strategy at the camel dairy farm because it increases selection intensity and decreases the generation interval. Using high milk-producing camels as donors and low producing camels as recipients, 146 embryos were recovered (6.1±1.0embryos/donor; range: 0-18). Embryos were transferred non-surgically into 111 recipients (83 single and 28 twin embryo transfers). Pregnancy rate at 21 days and 5 months was 55% (61/111) and 45% (50/111), respectively. Finally, a total of 46 recipients delivered a live calf. These results document the utility of embryo transfer using high milk producing dromedaries as donors.

Fertility after ovarian follicular wave synchronization and fixed-time natural mating compared to random natural mating in dromedary camels (Camelus dromedarius).

The objective of the study was to compare the efficiency of two ovarian follicular wave synchronization protocols coupled with fixed-time natural mating with that of random mating in dromedary camels. Dromedaries were assigned randomly to one of the three treatment groups. Group 1 animals (RM; n = 46) were mated randomly. Group 2 camels (1×GnRH-FTM; n = 46) were given a GnRH analog (Buserelin, 20 µg/animal, i.v.; Receptal, Intervet, Holland) at random, then were mated 14 days later. In Group 3 animals (2×GnRH-FTM; n = 41), random GnRH analog was followed by repeated GnRH injection 14 days later and fixed-time natural mating on Day 28. Transrectal examination and ultrasonography were performed at weekly intervals to evaluate ovarian follicular status, diagnose ovulation and pregnancy. Blood samples were collected for progesterone determination by ELISA to confirm ovulation and pregnancy. All female dromedaries were assigned randomly to one of thirteen fertile bulls and were bred once on Days 1, 14 and 28 in Groups 1-3, respectively. Ovarian follicular status and ovulation rate was similar among groups at the start of the study. Seventy-five of the 133 dromedaries (56.4%) ovulated after random natural mating or random GnRH treatment. Mean length of mating was 386 ± 17.8 (±SEM) seconds. There was no significant difference in mating time among groups and in pregnancy rate among dromedary bulls. In Group 3 (2×GnRH-FTM), ovarian follicular status before mating (P < 0.05), ovulation rate (n = 37, 90.2%, P < 0.001) and pregnancy rate at 21 and 60 days (PR 21 days n = 22, 53.7% and PR 60 days n = 19, 46.3%, P < 0.05) were greater compared to random natural mating (Group 1: OR n = 25, 54.3%, PR 21 days n = 13, 28.3% and PR 60 days n = 12, 26.1%). In Group 2 dromedaries (1×GnRH-FTM), treatment tended to improve follicular status before mating, ovulation rate (n = 34, 73.9%) and pregnancy rate at 21 and 60 days (PR 21 days n = 21, 45.7% and PR 60 days n = 16, 34.8%), but the effect was not significant compared to random natural mating. In conclusion, this is the first study demonstrating that favorable pregnancy rate can be achieved following ovarian follicular wave synchronization with repeated GnRH analog and fixed-time natural mating at 14 days intervals in dromedary camels.

Sleep disordered breathing in medically stable patients with myasthenia gravis.

We investigate sleep and breathing in clinically stable myasthenia gravis (MG) patients and ask weather sleep disordered breathing (SDB) is causally linked with MG. Nineteen MG patients with a mean disease duration of 9.7 years underwent sleep studies in two consecutive nights. The primary outcome measure was the respiratory disturbance index (RDI) in terms of snoring and apneas/hypopneas. Further outcome measurements were total sleep time, sleep stage distribution and the number of arousals. A clinically relevant SDB in terms of obstructive sleep apnea (OSA) (defined as RDI > 10/h) was found in four patients. There were only a few central apneas (central apnea index: 0.19 +/- 0.4/h). We did not find a relationship between maximum inspiratory pressure and SDB (r = -0.03). There is no evidence for a causal relationship between medically stable MG and SDB in terms of OSA. The extent of respiratory muscle weakness failed to correlate with SDB. Furthermore, our study does not confirm the high occurrence of central respiratory events during sleep in patients with well-controlled MG.

Influence of proportional assist ventilation on diaphragmatic activity in normal subjects.

In six awake healthy adults we studied the physiological effects of mechanical unloading of the respiratory muscles during increased ventilatory demand. We were interested in whether respiratory muscle activity is down regulated and if this is mainly a consequence of chemical factors, i.e. CO2-reduction, or non-chemical neuromuscular inhibition. With 33 mmHg inspiratory CO2 we induced modest hyperpnea of 24.4 +/- 3.9 L/min. Proportional assist ventilation (PAV) was applied with flow-related assist of 2.5 cm H2O/L/s and volume-related assist of 6 cm H2O/L. Respiratory muscle activity was measured by transdiaphragmatic pressure. Unloading caused a 57 percent reduction of the inspiratory transdiaphragmatic pressure-time product (p<0.05), while tidal volume, breathing frequency, and breathing pattern did not significantly change. These observations suggest that during increased ventilatory requirements, PAV results in down regulation of respiratory muscle activity and that this effect is mainly a consequence of neuromechanical inhibition.

Factors affecting plasma progesterone concentration and the retrospective determination of time of ovulation in cyclic mares.

Factors influencing plasma progesterone concentration were investigated in seven mares. Two-phase logistic curves were fitted (r=0.98) to plasma progesterone concentrations of blood samples collected once daily. In addition to the effect of time (P<0.001), there were differences (P<0.01) among mares in the peak height of the progesterone plateau and in the (area under the curve) AUC. Plasma progesterone concentrations were higher (P<0.001) after a multiple versus single ovulation. There was an effect of season (P<0.001), but no significant effect of luteal morphology. The retrospective determination of time of ovulation was carried out using a linear model on the seven mares and 25 additional mares. Linear regression on the measured values or on the ratio to the average concentration from D5 to D10, was calculated with the day of cycle between D0 and D4. The ovulation date was then calculated using both of these equations, whether blood sampling was performed twice or thrice weekly on 25 postpartum mares. The accuracy to predict day of ovulation (+/- 1 day) ranged from 88 to 97%. In conclusion, the retrospective estimation of time of ovulation in mares was possible, although the technique had some limitations.

Mechanical properties of glass-ceramic A-W-polyethylene composites: effect of filler content and particle size.

Composites which comprise a bioactive filler and ductile polymer matrix are desirable as implant materials since both their biological and mechanical properties can be tailored for a given application. In the present study three-point bending was used to characterise biomedical materials composed of glass-ceramic apatite-wollastonite (A-W) particulate reinforced polyethylene (PE) (denoted as AWPEX). The effects of filler volume fraction, varied from 10 to 50 vol%, and average particle size, 4.4 and 6.7 microm, on the bending strength, yield strength, mode of fracture, Young's modulus and strain to failure were investigated. HAPEX, a commercially used composite of hydroxyapatite and polyethylene, with a 40 vol% filler content, was used for comparison. Increasing the filler content caused an increase in Young's modulus, yield strength and bending strength, and a decreased strain to failure. When filler particle size was increased, the Young's modulus, yield and bending strengths were found to be slightly reduced. A transition in fracture behaviour from ductile to brittle behaviour was observed in samples containing between 30 and 40 vol% filler.

Bonding strength of the apatite layer formed on glass-ceramic apatite-wollastonite-polyethylene composites.

Bioactive glass-ceramic apatite-wollastonite (A-W) has been incorporated into polyethylene in particulate form to create new bioactive composites for potential maxillofacial applications. The effects of varying the volume fraction of glass-ceramic A-W filler and the glass-ceramic A-W particle size were investigated by measuring the bonding strength of the bonelike apatite layer formed on the surface of glass-ceramic A-W-polyethylene composites. The bonding strength was evaluated via a modified ASTM C-333 standard in which a tensile stress was applied to the substrate and the strength of the bioactive layer was compared with that formed on commercially available hydroxyapatite-polyethylene composite samples, HAPEX. The composites demonstrated greater bonding strength with increased filler content and reduced filler particle size (maximum 6.9 +/- 0.5 MPa) and a marginally greater bonding strength as compared with HAPEX (2.8 +/- 0.5 MPa), when glass-ceramic A-W-polyethylene composite samples with the same filler content were tested. The higher bonding strength of the apatite layer formed on the A-W-polyethylene composite samples suggests that, in addition to maxillofacial applications, these composites might also be utilized in applications involving higher levels of load bearing.

Apatite-forming ability of glass-ceramic apatite-wollastonite - polyethylene composites: effect of filler content.

The bioactivity of a range of glass-ceramic apatite-wollastonite (A-W) - polyethylene composites (AWPEXs) with glass-ceramic A-W volume percentages ranging from 10 to 50, has been investigated in an acellular simulated body fluid (SBF) with ion concentrations similar to those of human blood plasma. The formation of a biologically active apatite layer on the composite surface after immersion in SBF was demonstrated by thin-film X-ray diffraction (TF-XRD) and field-emission scanning electron microscopy (FE-SEM). An apatite layer was formed on all the composites, with the rate of formation increasing with an increase in glass-ceramic A-W percentage. For composites with glass-ceramic A-W filler contents >or=30 vol %, the apatite layer was formed within 12 h of immersion, which is a comparable time for apatite formation on monolithic glass-ceramic A-W. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) demonstrated that the apatite formation on AWPEX samples with 50 vol % filler content occurred in a manner similar to that seen on pure glass-ceramic A-W, in that the calcium, silicon, and magnesium ion concentrations increased and, conversely, a decrease was observed in the phosphate ion concentration. These results indicate that a suitable in vitro response was achieved on a composite incorporating particulate glass-ceramic A-W with a particularly favorable response being observed on the AWPEX sample with 50 vol % filler content.

Proportional positive airway pressure: a new concept to treat obstructive sleep apnoea.

Proportional positive airway pressure (PPAP) was designed to optimize airway pressure for the therapy of obstructive sleep apnoea (OSA). In a randomized crossover prospective study, the clinical feasibility of PPAP and its immediate effects on the breathing disorder and sleep in comparison with continuous positive airway pressure (CPAP) was evaluated. Twelve patients requiring CPAP therapy underwent CPAP and PPAP titration in a random order. Obstructive and mixed respiratory events could be completely abolished with both forms of treatment. This efficacy could be achieved at a significantly lower mean mask pressure during PPAP titration (8.45+/-2.42 cmH2O) compared to CPAP (9.96+/-2.7 cmH2O) (p=0.002). The mean minimal arterial oxygen saturation (Sa,O2) (82.8+/-6.5%) on the diagnostic night increased significantly (p<0.001) to an average Sa,O2 of 93.35+/-1.71% and 93.19+/-2.9% during CPAP and PPAP titration. Total sleep time, slow wave sleep and rapid eye movement (REM) sleep increased significantly by the same amount during both CPAP and PPAP titration (p<0.001), while sleep stage nonrapid eye movement (NREM) 1 and 2 decreased. Six patients preferred the PPAP titration night, four patients did not have a preference, and two patients preferred CPAP. The present data show that proportional positive airway pressure is as effective as continuous positive airway pressure in eliminating obstructive events and has the same immediate effect on sleep. The lower average mask pressure during proportional positive airway pressure implies potential advantages compared to continuous positive airway pressure. Proportional positive airway pressure presents a new effective therapeutic approach to obstructive sleep apnoea.

Effect of low-dose zearalenone exposure on luteal function, follicular activity and uterine oedema in cycling mares.

The effect of 10-day zearalenone administration starting 10 days after ovulation was studied in 6 cycling trotter mares in the summer period. After an entire oestrous cycle (Cycle 1), mares were given 7 mg purified zearalenone per os daily (1 mg/ml in ethyl alcohol) beginning on Day 10 of Cycle 2. Toxin exposure was continued until the subsequent ovulation. Luteal function and follicular activity were monitored daily by rectal palpation, ultrasonography and blood sampling for progesterone. During toxin exposure, all animals were in good physical condition. The toxin had no effect on the length of the interovulatory intervals, luteal and follicular phases. It did not influence significantly the plasma progesterone profiles (logistic curve parameters A1 to A6), the follicular activity (growth rate, maximum size of the ovulatory follicles, maximum number and the time of first increase in the number of large follicles) and the uterine oedema. It is concluded that in cyclic mares the methods used in this study could not detect any adverse effect of zearalenone (administered at a low dose similar to natural exposure) on reproduction.

Sodium lauryl sulfate increases the efficacy of a topical formulation of foscarnet against herpes simplex virus type 1 cutaneous lesions in mice.

The influence of sodium lauryl sulfate (SLS) on the efficacies of topical gel formulations of foscarnet against herpes simplex virus type 1 (HSV-1) cutaneous infection has been evaluated in mice. A single application of the gel formulation containing 3% foscarnet given 24 h postinfection exerted only a modest effect on the development of herpetic skin lesions. Of prime interest, the addition of 5% SLS to this gel formulation markedly reduced the mean lesion score. The improved efficacy of the foscarnet formulation containing SLS could be attributed to an increased penetration of the antiviral agent into the epidermis. In vitro, SLS decreased in a concentration-dependent manner the infectivities of herpesviruses for Vero cells. SLS also inhibited the HSV-1 strain F-induced cytopathic effect. Combinations of foscarnet and SLS resulted in subsynergistic to subantagonistic effects, depending on the concentration used. Foscarnet in phosphate-buffered saline decreased in a dose-dependent manner the viability of cultured human skin fibroblasts. This toxic effect was markedly decreased when foscarnet was incorporated into the polymer matrix. The presence of SLS in the gel formulations did not alter the viabilities of these cells. The use of gel formulations containing foscarnet and SLS could represent an attractive approach to the treatment of herpetic mucocutaneous lesions, especially those caused by acyclovir-resistant strains.

Multistep production of bioengineered skin substitutes: sequential modulation of culture conditions.

Many studies are being conducted to define the role of growth factors in cutaneous physiology in order to add cytokines in a timely fashion for optimal tissue engineering of skin. This study is aimed at developing a multistep approach for the production of bioengineered skin substitutes, taking into account the effects of various growth factors according to the culture time. The use of a serum-supplemented medium throughout the whole culture period of skin substitutes was compared to the sequential use of specific additives at defined culture steps. Histological analysis revealed that serum was necessary for keratinocyte proliferation and migration on dermal substitutes during the first 2 d after their seeding. However, the serum-free medium presented some advantages when supplemented with different additives at specific culture steps. Interestingly, ascorbic acid added to the dermal substitutes before and after keratinocyte seeding maintained their cuboidal morphology in the basal epidermal layer. In the absence of serum, collagen matrix degradation slowed down, and a better multilayered epidermal organization was obtained, notably with retinoic acid. Stratum corneum formation was also enhanced by fatty acids. Thus, sequential addition of exogenous factors to the medium used to produce skin substitutes can improve their structural features and functional properties in vitro.

In vitro and in vivo evaluations of sodium lauryl sulfate and dextran sulfate as microbicides against herpes simplex and human immunodeficiency viruses.

The efficacy of sodium lauryl sulfate (SLS), a sulfated anionic chaotropic surfactant, and dextran sulfate (DS), a polysulfated carbohydrate, against herpes simplex virus (HSV) and human immunodeficiency virus (HIV) infections was evaluated in cultured cells and in different murine models of HSV infection. Results showed that both SLS and DS were potent inhibitors of the infectivities of various HSV-1 and HSV-2 strains. Pretreatment of HIV-1 (strain NL4-3) with SLS also reduced its infectivity to 1G5 cells. DS prevented the binding of HSV to cell surface receptors and therefore its entry into cells. Pretreatment of HSV-1 (strain F) with 50 microM SLS resulted in a complete loss of virus infectivity to Vero cells. However, viruses were able to enter into cells and to produce in the nuclei capsid shells devoid of a DNA core. The amount of the glycoprotein D gene produced in these cells remained unchanged compared to controls, suggesting that SLS could interfere with the maturation of the virus. At a higher SLS concentration (100 microM), HSV was highly damaged by SLS pretreatment and only a few viral particles could enter into cells to produce abnormal capsids. Although DS was a more potent inhibitor of HSV infectivity in vitro, it was unable to provide any protection in murine models of HSV infection. However, SLS conferred a complete protection of animals infected cutaneously with pretreated viruses. In addition, skin pretreatment of mice with a polymer formulation containing SLS completely prevented the development of cutaneous lesions. More interestingly, intravaginal pretreatment of mice with SLS in a buffered solution also completely protected against lethal HSV-2 infection. Taken together, our results suggest that SLS could thus represent a candidate of choice as a microbicide to prevent the sexual transmission of HIV, HSV, and possibly other pathogens that cause sexually transmitted diseases.

Efficacies of topical formulations of foscarnet and acyclovir and of 5-percent acyclovir ointment (Zovirax) in a murine model of cutaneous herpes simplex virus type 1 infection.

The topical efficacies of foscarnet and acyclovir incorporated into a polyoxypropylene-polyoxyethylene polymer were evaluated and compared to that of 5% acyclovir ointment (Zovirax) by use of a murine model of cutaneous herpes simplex virus type 1 infection. All three treatments given three times daily for 4 days and initiated 24 h after infection prevented the development of the zosteriform rash in mice. The acyclovir formulation and the acyclovir ointment reduced the virus titers below detectable levels in skin samples from the majority of mice, whereas the foscarnet formulation has less of an antiviral effect. Reducing the number of treatments to a single application given 24 h postinfection resulted in a significantly higher efficacy of the formulation of acyclovir than of the acyclovir ointment. Acyclovir incorporated within the polymer was also significantly more effective than the acyclovir ointment when treatment was initiated on day 5 postinfection. The higher efficacy of the acyclovir formulation than of the acyclovir ointment is attributed to the semiviscous character of the polymer, which allows better penetration of the drug into the skin.

Relationship between thyroid function and seasonal reproductive activity in mares.

The relationship between thyroid function and seasonal reproductive activity in mares was investigated by comparing plasma triiodothyronine and thyroxine concentrations in anoestrous mares and in mares with cyclic ovarian activity during the anovulatory season. In study 1, the diurnal changes in plasma triiodothyronine and thyroxine concentrations on a single day were compared in anoestrous and cyclic mares. The mean thyroxine concentrations were significantly higher (P < 0.001) in the cyclic mares than in the anoestrous mares, whereas mean triiodothyronine concentrations were similar in both groups. In study 2, plasma thyroid hormone concentrations were monitored in mares that foaled before the vernal equinox. Nine mares resumed cyclic ovarian activity shortly after parturition and ten mares remained in anoestrus. Mean plasma triiodothyronine and thyroxine concentrations were significantly lower in the first 60-90 days after foaling in the mares undergoing anoestrus than in the mares undergoing normal ovarian activity after parturition (P < 0.001). In these mares, the increases in triiodothyronine and thyroxine concentrations were associated with the first ovulation after parturition. In study 3, thyroid hormone concentrations were monitored in adult (n=14) and young (n=14) mares. Mean thyroxine concentrations were significantly lower in adult anoestrous mares during the anovulatory period than in cyclic mares and in anoestrous mares before and after the anovulatory period (P < 0.01). Mean plasma triiodothyronine concentrations were also significantly lower (P < 0.001) in anoestrous mares from December until March. There were no significant differences between the plasma triiodothyronine and thyroxine concentrations in young cyclic and anoestrous mares. This relationship between thyroid function and expression of seasonal reproductive activity does not indicate that the thyroid gland is involved in the control of seasonality in horses. The decreased triiodothyronine and thyroxine concentrations in anoestrous mares may be the result of a hypothalamic control similar to that described for seasonal reproductive activity.

Physical characterization of the stratum corneum of an in vitro human skin equivalent produced by tissue engineering and its comparison with normal human skin by ATR-FTIR spectroscopy and thermal analysis (DSC).

An in vitro human skin equivalent may be obtained by culturing human keratinocytes on a collagen gel containing fibroblasts. The anchored skin equivalent cultured at the air-liquid interface closely resembles human skin and is acceptable for in vitro percutaneous absorption. However, it is still more permeable than human skin. Since intercellular lipids have been recognized to play an important role in skin permeability, infrared spectroscopy and differential scanning calorimetry were performed on the stratum corneum of bovine or human skin equivalents grown at different days of air-liquid culture. The symmetric and asymmetric CH(2) stretching vibrations suggested that for all days observed, the intercellular lipids were less organized than those in human skin, irrespective of whether bovine or human collagen was used. Different culture conditions were also tested and the medium without serum and no epidermal growth factor at the air-liquid culture showed results significantly more comparable to human skin. Actually, the thermal behavior of in vitro stratum corneum showed transitions at lower temperatures than human skin. The transition around 80 degrees C, in the form of a lipid-protein complex, was absent. These results showed that the structural arrangement of intercellular lipids and their thermodynamic properties hold a crucial role in the barrier function of the stratum corneum.