Study protocol: NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC trial): a randomised controlled trial.

INTRODUCTION: Congenital heart disease (CHD) is a major cause of infant mortality. Many infants with CHD require corrective surgery with most operations requiring cardiopulmonary bypass (CPB). CPB triggers a systemic inflammatory response which is associated with low cardiac output syndrome (LCOS), postoperative morbidity and mortality. Delivery of nitric oxide (NO) into CPB circuits can provide myocardial protection and reduce bypass-induced inflammation, leading to less LCOS and improved recovery. We hypothesised that using NO during CPB increases ventilator-free days (VFD) (the number of days patients spend alive and free from invasive mechanical ventilation up until day 28) compared with standard care. Here, we describe the NITRIC trial protocol. METHODS AND ANALYSIS: The NITRIC trial is a randomised, double-blind, controlled, parallel-group, two-sided superiority trial to be conducted in six paediatric cardiac surgical centres. One thousand three-hundred and twenty infants <2 years of age undergoing cardiac surgery with CPB will be randomly assigned to NO at 20 ppm administered into the CPB oxygenator for the duration of CPB or standard care (no NO) in a 1:1 ratio with stratification by age (<6 and ≥6 weeks), single ventricle physiology (Y/N) and study centre. The primary outcome will be VFD to day 28. Secondary outcomes include a composite of LCOS, need for extracorporeal membrane oxygenation or death within 28 days of surgery; length of stay in intensive care and in hospital; and, healthcare costs. Analyses will be conducted on an intention-to-treat basis. Preplanned secondary analyses will investigate the impact of NO on host inflammatory profiles postsurgery. ETHICS AND DISSEMINATION: The study has ethical approval (HREC/17/QRCH/43, dated 26 April 2017), is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617000821392) and commenced recruitment in July 2017. The primary manuscript will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ACTRN12617000821392.

Restricting vitamin A intake increases bone formation in Zambian children with high liver stores of vitamin.

This analysis was performed in Zambian children who had a high prevalence of hypervitaminosis A, defined as > 1.0 µmol retinol/g liver. Bone parameters included markers of bone formation (P1NP), bone resorption (CTX), parathyroid hormone, calcium, vitamin A, and vitamin D. Low dietary vitamin A intake increased P1NP. PURPOSE: Vitamin A (VA) interacts with bone health, but mechanisms require clarification. In countries where multiple interventions exist to eradicate VA deficiency, some groups are consuming excessive VA. Bone metabolism and inflammatory parameters were measured in Zambian children who had high prevalence of hypervitaminosis A determined by 13C-retinol isotope dilution. METHODS: Children (n = 143), 5 to 7 years, were recruited into a placebo-controlled biofortified orange maize feeding study for 90 days. Bone turnover (P1NP and CTX) and inflammatory (C-reactive protein (CRP) and alpha-1-acid glycoprotein) biomarkers were measured in fasting blood samples before and/or after intervention with the following: (1) VA at the recommended dietary allowance (400 µg retinol activity equivalents/day (as retinyl palmitate)), (2) maize enhanced with the provitamin A carotenoid ß-carotene (2.86 mg/day), or (3) a placebo. Parathyroid hormone, calcium, and 25(OH)-vitamin D were measured at end line. RESULTS: Bone formation, as measured by P1NP, increased (P < 0.0001) in the placebo group who consumed low preformed VA during the intervention. Bone resorption, measured by CTX, was not affected. P1NP and CTX were negatively associated with inflammation, most strongly with CRP. Serum calcium did not differ among groups and was low (7.29 ± 0.87 µg/dL). Serum 25(OH) D did not differ among groups (54.5 ± 15 nmol/L), with 91% < 75 nmol/L and 38% < 50 nmol/L. CONCLUSIONS: Reduction of dietary preformed VA in Zambian children for 4 months improved bone formation. Chronic consumption of preformed VA caused hypervitaminosis A and may impair bone formation. In children, this could be associated with failure to accrue optimal peak bone mass. TRIAL REGISTRATION: The NIH Clinical Trial registry number is NCT01814891; https://clinicaltrials.gov/ct2/show/NCT01814891 .

Hypercarotenodermia in Zambia: which children turned orange during mango season?

Vitamin A (VA) deficiency is a public health problem in many countries. The World Health Organization recommends high-dose VA supplements to children aged 6-59 months based on unequivocal evidence that supplements decreased mortality risk. VA supplements were meant as a temporary intervention until more sustainable approaches could be implemented. Fortification of processed foods with preformed VA is a means to improve VA status. The most recent addition of retinyl palmitate to cooking oil in countries that may also fortify margarine and milk will undoubtedly have a positive impact on VA status. However, quantitative measures have not been used to assess the underlying VA status of the groups who have adopted widespread fortification. The addition of preformed VA to otherwise adequate diets in VA may cause excessive total body stores. Monitoring population status will require accurate VA assessment to ensure that hypervitaminosis does not prevail. This perspective describes a cohort of rural Zambian children who have adequate diets in VA, mostly as provitamin A carotenoids; who were given high-dose VA supplements till the age of 5 years; who have access to VA-fortified sugar; and whose mothers had access to VA-fortified sugar throughout pregnancy and lactation. Many of these children turned orange during mango season, and this phenomenon occurred at estimated liver reserve concentrations >1 µmol retinol equivalents/g liver. It will be necessary to continue to monitor VA status, including all sectors of the population that have access to successful interventions, to optimize health with the intent to lower retinol content of fortified foods or better target VA supplementation to areas of most need.

Estimating the extra cost of living for people with disabilities.

Addressing the extra economic costs of disability is a logical step towards alleviating elements of social exclusion for people with disabilities. This study estimates the long-run economic cost of disability in Ireland in terms of the additional spending needs that arise due to disability. It defines and estimates models of the private costs borne by families with individuals who have a disability in Ireland when compared with the wider population, both in general and by severity of disability. Our modelling framework is based on the standard of living approach to estimating the cost of disability. We extend on previous research by applying panel ordered probit models to living in Ireland survey data 1995-2001 in order to control for the effects of previous disability and income and correlated unobserved heterogeneity. The approach allows us to quantify, for the first time, the additional long-run economic costs of living associated with disability. Our findings suggest that the extra economic cost of disability in Ireland is large and varies by severity of disability, with important implications for measures of poverty.

Method for bacteriophage isolation against target Campylobacter strains.

AIMS: Poultry meat is considered a major source of Campylobacter. This micro-aerobic bacterium is commonly responsible for foodborne illness. This work focuses on the isolation of Campylobacter coli lytic bacteriophages (phages) against target C. coli strains. METHODS AND RESULTS: A method involving the enrichment of free-range chicken samples in a broth containing the target C. coli strains and salts (CaCl(2) and MgSO(4)) was used for phage isolation. This method allowed the isolation of 43 phages that were active against 83% of the C. coli strains used in the isolation procedure. Approximately 65% of the phages were also effective against Campylobacter jejuni strains. CONCLUSIONS: The use of target pathogens in the phage isolation step improves the likelihood of detecting and isolating phages for the control of these specific strains. SIGNIFICANCE AND IMPACT OF THE STUDY: This technique will be valuable in the context of phage therapy for enriching for phages that are active against specifically identified strains of bacteria, for example from a food poisoning outbreak or epidemic strains resistant to multiple antibiotics. In these situations, using the conventional methods for searching for bacteriophages active for these particular strains can be a time-consuming, if not an unsuccessful process. Using the isolation method described in this manuscript, the particular strains can be added to the enrichment broth increasing the probability of finding phages against them. Therefore, it will shorten the time needed for seeking phages able to lyse target strains, which in most of the cases, because of the rapid increase in antimicrobial-resistant bacteria, is of crucial importance.

Economic consequences of falls and fractures among older people.

This paper uses a burden of illness methodology to achieve a better understanding of the cost of falls and fractures within Ireland. The base number of older people falling annually in Ireland is 130,000. About 80% of these are non-injurious with the remainder following a healthcare trajectory that may involve hospital care, GP visits, outpatient visits, informal care, long-stay care and sometimes death. Unit costs are applied to the different levels of care and aggregated to generate the overall cost of illness of falls and fractures in the country. The estimated baseline cost of falls and fractures is Euro 404 million. The largest components of this cost are: mortality, lost quality of life, long-stay care costs and hospital inpatient costs. The findings are relevant in the context of the development of a National Strategy for the prevention of falls and fractures in Ireland. Investment in such a Strategy will likely yield significant benefits.

Wide variation in effectiveness of laboratory disinfectants against bacteriophages.

AIMS: The purpose of this study was to identify an effective disinfectant for the inactivation of the bacteriophages (phages) being used in our laboratory, as published studies on phage inactivation are far from unanimous in their conclusions. METHODS AND RESULTS: The phages studied were three closely related strains of Myoviridae and three strains of Siphoviridae. Three disinfectants which are used commonly in microbiology laboratories were evaluated: Virkon (1%), ethanol (75%) and sodium hypochlorite (2500 ppm available chlorine). The most effective of these was Virkon, which inactivated all six phages rapidly. Ethanol was effective against the Myoviridae but had little effect on the Siphoviridae. Sodium hypochlorite was the least effective of the disinfectants evaluated. CONCLUSIONS: The findings of this study demonstrate a wide diversity in the effectiveness of disinfectants tested for inactivation of phages. SIGNIFICANCE AND IMPACT OF THE STUDY: Of the disinfectants tested Virkon is the most suitable choice for those unable to carry out disinfection validation studies, or where a broad spectrum disinfectant against phages is required. All of the phages in this study showed resilience to inactivation by sodium hypochlorite, and therefore this disinfectant is an unwise choice for use against phage without first assessing its effectiveness.

Survival rate of airborne Mycobacterium bovis.

Despite years of study the principle transmission route of bovine tuberculosis to cattle remains unresolved. The distribution of pathological lesions, which are concentrated in the respiratory system, and the very low dose of Mycobacterium bovis needed to initiate infection from a respiratory tract challenge suggest that the disease is spread by airborne transmission. Critical to the airborne transmission of a pathogenic microorganism is its ability to survive the stresses incurred whilst airborne. This study demonstrates that M. bovis is resistant to the stresses imposed immediately after becoming airborne, 94% surviving the first 10 min after aerosolisation. Once airborne the organism is robust, its viability decreasing with a half-life of approximately 1.5 hours. These findings support the hypothesis that airborne transmission is the principle route of infection for bovine tuberculosis.

The phosphorus budget of the Thame catchment, Oxfordshire, UK: 1. Mass balance.

The relative magnitudes of annual diffuse and point source loads of phosphorus (P) to the River Thame were estimated from daily and monthly measurements of discharge and concentration. Existing data from gauging and monitoring sites on the river network and at point sources were supplemented by survey data at a range of spatial scales. Results showed that during low flow periods most of the P could be attributed to point sources, while at high flows the figure was less than 10%. The introduction of P stripping at Aylesbury, a major sewage treatment works in the catchment, was estimated to have reduced the annual load of P from the sewage treatment works by approximately 45 t, with a similar reduction in loss from the catchment. This gave a reduction in low flow concentrations of soluble reactive phosphorus (SRP) from 2.5 to 1.7 mg l(-1). Concentrations of SRP in river water remain above eutrophication thresholds because of the influence of other STWs in the catchment and insufficient natural discharge to dilute this.

The phosphorus budget of the Thame catchment, Oxfordshire: 2. Modelling.

The phosphorus budget of the River Thame was modelled at a daily time scale, using estimates of diffuse and point source contributions of discharge. The model simulated suspended sediment (SS), soluble unreactive phosphorus (SUP), soluble reactive phosphorus (SRP) and particulate phosphorus (PP) concentrations within the main river and major tributaries. Diffuse source estimates of phosphorus loads were based on characteristic losses from identified main landscape classes, with hydrology described by a simple conceptual storage model. In-stream flow was modelled using a kinematic wave equation. Transfer of suspended sediment and phosphorus components was approximated by advection. In-stream sources and sinks included uptake and release of soluble reactive phosphorus by bed sediment, instant equilibration between SRP and the PP concentration on suspended sediment, and flow-related entrainment and deposition of suspended sediment. Simulations at sites within the catchment were compared with measurements made in 1998-1999. Results showed the P budget is dominated by mixing of diffuse and point source water, but some within-river processes have been shown to be capable of significantly influencing SRP concentrations. The development of a sediment entrainment and deposition component of the model has proved particularly valuable in emulating the hysteretic relationship between discharge and suspended sediment concentration in the river. It also provides a measure of available bed sediment.

Changes in intrafollicular pressure in the rat ovary by nitric oxide and by alteration of systemic blood pressure.

BACKGROUND: ovulation is associated with degradation of the follicular apex vasodilatation and increased permeability of ovarian vessels. These changes may maintain or increase intrafollicular pressure (IFP) at ovulation to cause rupture of the follicular wall. OBJECTIVE: to investigate the possible regulation of IFP during the ovulatory process. STUDY DESIGN: immature Sprague-Dawley rats were primed with pregnant mare serum gonadotrophin (PMSG; 10IU) and given hCG (10IU) 48h later. The ovary was exposed 48-60h after PMSG, micropipette inserted into the Graafian follicle and the IFP measured at three time periods: preovulatory (PO) 48h after PMSG; midovulatory (MO) 4-7h after hCG; late ovulatory (LO) 9-12h after hCG. The offset of the nitric oxide synthase (NOS) inhibitor L-arginine methyl ester (L-NAME), the alpha(1)-adrenoceptor agonist phenylephrine and the beta-adrenoceptor agonist isoprenaline were tested. RESULTS: phenylephrine given i.v. increased the systemic blood pressure, and significantly decreased the IFP in the LO phase (78% of pre-treatment value). Local administration of phenylephrine or isoprenaline (1ml of 1.5-15 microM) by superfusion over the ovary did not change the IFP. Local administration of L-NAME (1ml of 2 microM) significantly lowered (P<0.05) the IFP in the MO and LO phases, but was without effect in the PO phase. CONCLUSION: this study reveals that IFP regulation may be related to changes of the systemic blood pressure and that NO may be one local ovarian mediator in IFP regulation.

Effect of carbon dioxide on the Oriental cockroach Blatta orientalis.

Exposure to high concentrations of carbon dioxide (CO2) killed adult and nymphal stages of the oriental cockroach Blatta orientalis L. (Dictyoptera: Blattidae) with LT50 values of 11.5-16.2 h for 60% CO2 in air and 5.7-7.1 h for 100% CO2 at 20 degrees C; corresponding LT50s at 28 degrees C were 2.8-4.6 h for 60% CO2 in air and 2.3-3.6 h for 100% CO2. Complete kill of mobile stages was obtained within 24 h using 60% CO2 at 20 degrees C. Survivors of treatments with 100% CO2 at 28 degrees C remained completely paralysed for up to 3 days post-treatment and took up to 5 days to regain normal movement, but adult females then resumed production of oothecae with no significant loss in fecundity. Oothecae 5 or 30 days after deposition required 60-84 h exposure to 60% CO2 at 20 degrees C to prevent emergence of nymphs but less time using 100% CO2 at 28 degrees C. At 28 degrees C, when adult females were treated with 100% CO2 and 52% r.h. for 6 h (giving 100% mortality) loss of weight was significantly greater than that following treatment with air at 52% r.h. for 6 h (giving no mortality). However, significantly greater weight loss also occurred when they were treated with dried air (< 10% r.h.) for 6 h, also with no mortality. The toxicity of CO2 to mobile stages of the oriental cockroach appeared to result from irreversible effects on the nervous system, rather than from water loss during exposure.

Novel method for intrafollicular pressure measurements in the rat ovary: increased intrafollicular pressure after hCG stimulation.

The ovulatory process in the rat comprises a period of about 12-15 h, from the time of the preovulatory LH surge to follicular rupture and extrusion of the oocyte. Follicular rupture is most likely caused, at least in part, by decreased tensile strength at the follicular apex due to degradation of collagen fibres of the extracellular matrix. It has been debated whether changes in intrafollicular pressure occur during the ovulatory process and whether such changes facilitate rupture of the follicle. In the present study, rats were primed with equine chorionic gonadotrophin (eCG, 10 iu) followed by hCG (10 iu) 48 h later. The intrafollicular pressure in the preovulatory follicle was recorded during 1 h at distinct time phases of the ovulatory process by use of an active servo-null pressure system based on the proportionality between electrical resistance and pressure within the tip of an inserted micropipette. The basal intrafollicular pressure was 16.6 +/- 1.0 mm Hg at the preovulatory phase (48 h after eCG) and increased gradually throughout the ovulatory process to 21.4 +/- 2.4 mm Hg at 4-7 h after hCG (mid-ovulatory phase) and 23.9 +/- 1.9 mm Hg at 8-12 h after hCG (late ovulatory phase; significantly higher (P < 0.01) than the preovulatory phase). Short-term peaks of increased pressure, possibly representing contractility, were not detected in follicles of the preovulatory phase, but were seen in most follicles of the mid- and late ovulatory phases. The mean amplitude of the short-term pressure increases was 12.3 +/- 3.2 mm Hg and the increases occurred at intervals of 24.7 +/- 3.6 s. These short-term increments in intrafollicular pressure were still present after hysterectomy had been performed. The wall tension index was calculated by measuring the follicular size and estimating the thickness of the follicle wall. The index increased from 93.9 +/- 13.3 at the preovulatory phase to 207.3 +/- 47.7 (mid-ovulatory phase) and to significantly higher values at the late ovulatory phase (320.9 +/- 33.5). In conclusion, this study shows that there is an increase in intrafollicular pressure in the ovulating follicle of the rat ovary during the late stages of the ovulatory process, and that short-term increases in intrafollicular pressure occur during the late phase of the ovulatory process. These changes in pressure may be essential for follicular rupture to proceed normally.

Recruiting problem-based learning (PBL) tutors for a PBL-based curriculum: the Flinders University experience.

OBJECTIVES: To examine the contribution made to problem-based learning (PBL) by individual teachers and by departments in years 1 and 2 of a new graduate-entry medical programme (GEMP) with a PBL-based curriculum. METHODS: We compiled a database on all PBL tutoring undertaken in years 1 and 2 during the first 3 years in which the GEMP was delivered. This allowed us to quantify and analyse the contribution made by individuals and by departments. RESULTS: At 3 years following introduction of the GEMP, 136 (25.9%) of the school's 525 staff had trained as PBL tutors and 98 (18.7%) had tutored. Both individuals and departments differed greatly in the amount of time devoted to PBL tutoring. Staff who tutored once tended to tutor again in subsequent years. Compared with staff in clinical departments, those in non-clinical departments (who constituted 12% of the total) made a greater relative contribution though a smaller absolute contribution to tutoring. CONCLUSIONS: These findings prompted us to develop a formula that distributes the PBL tutoring load more evenly across departments. This was successfully introduced in 1999. It recognizes the fact that only a minority of staff will volunteer to become PBL tutors. Strategies that might encourage more staff to tutor are briefly discussed.

Role of specific apoptotic pathways in the restoration of paclitaxel-induced apoptosis by valspodar in doxorubicin-resistant MCF-7 breast cancer cells.

Paclitaxel (Taxol) kills tumor cells by inducing both cellular necrosis and apoptosis. A major impediment to paclitaxel cytotoxicity is the establishment of multidrug resistance whereby exposure to one chemotherapeutic agent results in cross-resistance to a wide variety of other drugs. For example, selection of MCF-7 breast cancer cells for resistance to doxorubicin (MCF-7ADR cells) results in cross-resistance to paclitaxel. This appears to involve the overexpression of the drug transporter P-glycoprotein which can efflux both drugs from tumor cells. However, MCF-7ADR cells possess a deletion mutation in p53 and have considerably reduced levels of the Fas receptor, Fas ligand, caspase-2, caspase-6, and caspase-8, suggesting that paclitaxel resistance may also stem from a bona fide block in paclitaxel-induced apoptosis in these cells. To address this issue, we examined the ability of the P-glycoprotein inhibitor valspodar to restore paclitaxel accumulation, paclitaxel cytotoxicity, and paclitaxel-induced apoptosis. Compared to drug sensitive MCF-7 cells, MCF-7ADR cells accumulated >6-fold less paclitaxel, were approximately 100-fold more resistant to killing by the drug, and were highly resistant to paclitaxel-induced apoptosis. In contrast, MCF-7ADR cells pretreated with valspodar were indistinguishable from drug-sensitive cells in their ability to accumulate paclitaxel, in their chemosensitivity to the drug, and in their ability to undergo paclitaxel-induced apoptosis. Valspodar, by itself, did not affect these parameters. This suggests that the enhancement of paclitaxel toxicity in MCF-7ADR cells involves a restoration of apoptosis and not solely through enhanced drug-induced necrosis. Morever, it appears that changes in the levels/activity of p53, the Fas receptor, Fas ligand, caspase-2, caspase-6, or caspase-8 activity have little effect on paclitaxel-induced cytotoxicity and apoptosis in human breast cancer cells.

The measurement of endometrial perfusion in norplant users: a pilot study.

The use of progestogens without oestrogen is commonly associated with irregular menstrual bleeding. Oestrogens and progestogens are both thought to influence endometrial perfusion; changes in endometrial perfusion may contribute to vascular fragility and breakdown. In this study, endometrial perfusion was measured using laser-Doppler fluxmetry in women in the secretory phase of the menstrual cycle before and 4-6 weeks after insertion of the low-dose long-acting levonorgestrel contraceptive implant system, Norplant. Endometrial perfusion was also measured in women exposed to Norplant for up to 19 months. There was no significant difference between endometrial perfusion in control cycles (27.2 flux units +/- 5.5, SEM) and at 4-6 weeks after Norplant insertion (16.3 flux units +/- 5.0), a time when irregular bleeding and spotting are common. Endometrial perfusion was no different from controls after longer periods of Norplant exposure (35.7 flux units +/- 7.2). No direct relationships between endometrial perfusion and plasma concentrations of ovarian steroid hormones were demonstrated. Short-term endometrial vasomotion was largely abolished during Norplant exposure.

Do African Americans have lower energy expenditure than Caucasians?

OBJECTIVE: To review current studies that examine differences in energy expenditure between African Americans and Caucasians as possible modulators of attained differences in overweight status. DESIGN: Literature review of recent clinical and laboratory studies. METHODS: Studies chosen for review were those that examined directly resting metabolic rate (RMR), using indirect calorimetry, and total daily energy expenditure (TDEE) and physical activity energy expenditure (PAEE), using doubly labeled water. RESULTS: Ten of 15 studies reviewed reported a lower RMR in African Americans than in Caucasians. The differences in RMR between African Americans and Caucasians ranged from 81 to 274 kcal/day and could not be explained by differences in age, fat-free mass (FFM) or methodological concerns. Two of six studies of energy expenditure using doubly labeled water suggest that Black adults have a tendency for lower TDEE that can be accounted for primarily by a lower PAEE. CONCLUSIONS: If future studies indicate conclusively that African Americans do have lower RMR, TDEE and PAEE than Caucasians, then the disproportionally higher risk of obesity and associated metabolic disorders in Black adults may be preventable-especially in Black women. If these race differences are indeed a result of both physiological and behavioral factors, then interventions designed to reduce caloric intake and/or increase energy expenditure through lifestyle activity or structured exercise programs become especially important for African Americans and should be encouraged. International Journal of Obesity (2000)24, 4-13

The immunohistochemical response of the rat periodontal ligament endothelium to an inflammatory stimulus.

Recently, inflammation has been recognised as an important co-requisite to orthodontic tooth movement. When such a reaction is initiated, the process of up-regulation of certain adhesion molecules may occur, resulting in the extravasation of leukocytes. This may stimulate progenitor/precursor pathways and signals that regulate the biological responses resulting in tooth movement. We propose that up-regulation of leukocyte adhesion molecules occurs in response to orthodontic forces, resulting in circulating monocyte attraction, extravasation and differentiation into osteoclasts, which are responsible for bone resorption that results in orthodontic tooth movement. To investigate this hypothesis, it is necessary to determine whether periodontal ligament (PDL) endothelium responds to inflammatory stimuli as other organs do. We studied the normal distribution of endothelial adhesion molecule ICAM-1 within PDL vessels, and then the following exposure to an inflammatory endotoxin. The rat PDL blood vessels expressed ICAM-1 in response to the inflammatory stimulus, similar to other organs, suggesting that the inflammatory responses are similar. Whether and where in the PDL microvascular bed orthodontic forces cause up-regulation of ICAM-1 needs to be established.

Theophylline or caffeine: which is best for apnea of prematurity?

Apnea of prematurity is a common problem of the premature infant under 30 weeks gestation. Theophylline and caffeine, two methylxanthines, are widely used to treat this condition. The drugs are equally effective in preventing apnea in the premature infant. Caffeine citrate has many advantages over theophylline, however, including once-a-day dosing, more predictable plasma concentrations, earlier onset of action, and minimal side effects. Caffeine is therefore the initial drug of choice for apnea of prematurity.

Aquaporin-1 expression in visceral smooth muscle cells of female rat reproductive tract.

The aquaporins (AQ-s) are a group of intrinsic membrane proteins which facilitate movement of water across cell membranes; their recent identification in the kidney has led to the reappraisal of the mechanisms and pathways of water movement across epithelia. Aquaporin-1, (CHIP-28) is reported distributed in cardiac myocytes and vascular smooth muscle cells of large arteries. A related protein, AQ-4, has been identified in the sarcolemma of skeletal muscle fibres. We report aquaporin expression in the cell membrane of smooth muscle cells of the rat genital tract; fluorescence immunohistochemistry of rat uterine (fallopian) tube and vagina demonstrated AQ-1 in visceral smooth muscle of these tissues. In the uterine tube, AQ-1 labelling is most pronounced in the innermost longitudinal and the inner cells of the circular muscle layer and is absent from the outer longitudinal muscle layer of the myosalpinx. The possibility of a specific role for AQ-1 in tubal transport by altering the tubal luminal diameter during the estrus cycle is suggested.