Feeding olive cake silage up to 20% of DM intake in sheep improves lipid quality and health-related indices of milk and ovine halloumi cheese.

This study aimed to evaluate the use of a by-product, olive cake silage (OCS), as a forage replacement in sheep diets for the improvement of fatty acid (FA) content of milk and thus, the lipids of the ovine halloumi cheese produced. Sixty second-parity purebred Chios ewes in mid-lactation were assigned to three diet treatments (2 lots of 10 animals per treatment) receiving 0%, 10%, and 20% of OCS on dry matter basis for 3 weeks (treatments S0, S10, and S20, respectively). Halloumi cheese was manufactured from fresh raw milk of ewes fed the three different diets. Inclusion of OCS in the diets increased linearly the concentration in milk of unsaturated FA up to 20%, monounsaturated FA up to 23%, polyunsaturated FA up to 11%, rumenic acid (CLA cis-9, trans-11) up to 61%, and consequently reduced the atherogenicity and thrombogenicity milk indices by 31% and 27%, for the S10 and S20 treatments, respectively, compared with the control treatment. Moreover, these differences were carried over to the lipid profile of ovine halloumi cheese showing, on average, more than 25% increase of unsaturated, polyunsaturated, and monounsaturated FA, with particularly enhanced oleic and rumenic acid content. These changes resulted in reduced atherogenicity by 29% and 45% and thrombogenicity by 23% and 24% of ovine halloumi cheese made from milk of S10 and S20 diets, respectively. Milk yield, milk fat, or protein content was not affected by S10 or S20 feeding treatments compared to control. Overall, the applied ensiling method of olive cake produces a by-product that can be included as a forage replacement up to 20% of DM intake in Chios sheep without adversely affecting the lactating performance. Furthermore, the present study showed that such substitution improves the lipid quality of milk and related halloumi cheese enriching these ovine dairy products with beneficial to human health fatty acids.

The use of ensiled olive cake in the diets of Friesian cows increases beneficial fatty acids in milk and Halloumi cheese and alters the expression of SREBF1 in adipose tissue.

This study aimed to evaluate the effect of dietary inclusion of ensiled olive cake, a by-product of olive oil production, on milk yield and composition and on fatty acid (FA) profile of milk and Halloumi cheese from cows. Furthermore, the effect of olive cake on the expression of selected genes involved in mammary and adipose lipid metabolism was assessed in a subset of animals. A total of 24 dairy cows in mid lactation were allocated into 2 isonitrogenous and isoenergetic feeding treatments, named the control (CON) diet and the olive cake (OC) diet, in which part of the forages (alfalfa, barley hay, and barley straw) were replaced with ensiled OC as 10% of dry matter according to a 2 × 2 crossover design with two 28-d experimental periods. At the end of the second experimental period, mammary and perirenal adipose tissue samples were collected from 3 animals per group for gene expression analysis by quantitative reverse-transcription PCR. The expression of 11 genes, involved in FA synthesis (ACACA, FASN, G6PDH), FA uptake or translocation (VLDLR, LPL, SLC2A1, CD36, FABP3), FA saturation (SCD1), and transcriptional regulation (SREBF1, PPARG), was evaluated. No significant differences were observed between groups concerning milk yield, fat percentage, protein percentage, and protein yield (kg/d), whereas milk fat yield (kg/d) increased in the OC group. Dietary supplementation with ensiled OC modified the FA profile of milk and Halloumi cheese produced. There was a significant decrease in the concentration of de novo synthesized FA, saturated FA, and the atherogenic index, whereas long-chain and monounsaturated FA concentration was increased in both milk and cheese. Among individual saturated FA, only stearic acid was elevated, whereas among individual monounsaturated FA, increments of oleic acid (C18:1 cis-9) and the sum of C18:1 trans-10 and trans-11 acids were demonstrated in milk and Halloumi cheese produced. Although no diet effect was reported on total polyunsaturated FA, the concentration of CLA cis-9,trans-11 was increased in both milk and Halloumi cheese fat of the OC group. The expression of the genes tested was unaffected apart from an observed upregulation of SREBF1 mRNA expression in perirenal fat from cows fed the OC diet. Milk FA differences observed were not associated with alterations in mammary expression of genes involved in FA synthesis, uptake, translocation, and regulation of lipogenesis. Overall, the inclusion of ensiled OC in cow diets for a 4-wk period improved, beneficially for human health, the lipid profile of bovine milk and Halloumi cheese produced without adversely affecting milk yield and composition or the expression of genes involved in lipid metabolism of mammary and adipose tissues in cows.

Variants in the 3' untranslated region of the ovine acetyl-coenzyme A acyltransferase 2 gene are associated with dairy traits and exhibit differential allelic expression.

The acetyl-CoA acyltransferase 2 (ACAA2) gene encodes an enzyme of the thiolase family that is involved in mitochondrial fatty acid elongation and degradation by catalyzing the last step of the respective ß-oxidation pathway. The increased energy needs for gluconeogenesis and triglyceride synthesis during lactation are met primarily by increased fatty acid oxidation. Therefore, the ACAA2 enzyme plays an important role in the supply of energy and carbon substrates for lactation and may thus affect milk production traits. This study investigated the association of the ACAA2 gene with important sheep traits and the putative functional involvement of this gene in dairy traits. A single nucleotide substitution, a T to C transition located in the 3' untranslated region of the ACAA2 gene, was used in mixed model association analysis with milk yield, milk protein yield and percentage, milk fat yield and percentage, and litter size at birth. The single nucleotide polymorphism was significantly associated with total lactation production and milk protein percentage, with respective additive effects of 6.81 ± 2.95 kg and -0.05 ± 0.02%. Additionally, a significant dominance effect of 0.46 ± 0.21 kg was detected for milk fat yield. Homozygous TT and heterozygous CT animals exhibited higher milk yield compared with homozygous CC animals, whereas the latter exhibited increased milk protein percentage. Expression analysis from age-, lactation-, and parity-matched female sheep showed that mRNA expression of the ACAA2 gene from TT animals was 2.8- and 11.8-fold higher in liver and mammary gland, respectively. In addition, by developing an allelic expression imbalance assay, it was estimated that the T allele was expressed at an average of 18% more compared with the C allele in the udder of randomly selected ewes. We demonstrated for the first time that the variants in the 3' untranslated region of the ovine ACAA2 gene are differentially expressed in homozygous ewes of each allele and exhibit allelic expression imbalance within heterozygotes in a tissue-specific manner, supporting the existence of cis-regulatory DNA variation in the ovine ACAA2 gene. This is the first study reporting differential allelic imbalance expression of a candidate gene associated with milk production traits in dairy sheep.

Pharmacological assessment of ibuprofen arginate on platelet aggregation and colon cancer cell killing.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, are amongst the most commonly used medications and produce their anti-inflammatory and analgesic benefits by blocking cyclooxygenase (COX)-2. These drugs also have the potential to prevent and treat cancer and some members of the class including ibuprofen can produce anti-platelet effects. Despite their utility, all NSAIDs are associated with increased risk of cardiovascular side effects which our recent work suggests could be mediated by increased levels of the endogenous NO synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) leading to reduced endothelial NOS activity and associated endothelial cell dysfunction. ADMA is a cardiotoxic hormone and biomarker of cardiovascular risk whose effects can be prevented by l-arginine. The ibuprofen salt, ibuprofen arginate (Spididol®) was created to increase drug solubility but we have previously established that it not only effectively blocks COX-2 but also provides an arginine source able to reverse the effects of ADMA in vitro and in vivo. Here we have gone on to explore whether the formulation of ibuprofen with arginine influences the potency and efficacy of the parent molecule using a range of simple in vitro assays designed to test the effects of NSAIDs on (i) platelet aggregation and (iii) colon cancer cell killing. Our findings demonstrate that ibuprofen arginate retains these key functional effects of NSAIDs with similar or increased potency compared to ibuprofen sodium, further illustrating the potential of ibuprofen arginate as an efficacious drug with the possibility of improved cardiovascular safety.

Induction of DNA damage and caspase-independent programmed cell death by vitamin E.

Vitamin E comprises 8 functionally unique isoforms and may be a suitable candidate for the adjuvant treatment of prostate cancer. In this study, we examined the ability of 2 vitamin E isoforms [α-tocotrienol (γ-TT) and δ-tocotrienol (δ-TT)] and 4 synthetic derivatives [γ- and δ-tocotrienol succinate (γ-TS, δ-TS), α-tocopheryl polyethylene glycol succinate (TPGS), and α-tocopheryl polyethylene glycol ether (TPGS-e)] of vitamin E to induce cell death in AR- (DU145 and PC-3) and AR+ (LNCaP) prostate cancer cell lines. Our results show that δ-TT and TPGS-e are the most effective isoform and synthetic derivative, respectively, of all compounds examined. Overall, the results of our study suggest that isoforms and synthetic derivatives of vitamin E have the potency to trigger both caspase-dependent and -independent DNA damage and dominant caspase-independent programmed cell death. The capacity of vitamin E to trigger caspase-independent programmed cell death suggests that it may be useful in the chemotherapy of prostate cancer since it may prevent the tumor resistance commonly associated with the use of classical chemotherapeutic agents that trigger caspase-dependent programmed cell death.

Caspase-independent pathways of programmed cell death: the unraveling of new targets of cancer therapy?

In the past few years, accumulating evidence in the literature supports the existence of pathways of caspase-independent programmed cell death (CI-PCD). These pathways are likely to be acting as 'death backup systems' that ensure effective removal of defective cells from the organism. Similar to classical apoptosis i.e. caspase-dependent programmed cell death (CD-PCD), the mitochondrion is the main organelle orchestrating the series of events which are required for the induction of CI-PCD. In addition, the pro-apoptotic proteins Bax and Bid are also key participants in CI-PCD. However, contrary to CD-PCD, CI-PCD involves executioners other than the caspases which include the cathepsins, the calpains and serine proteases. The protein AIF may also play an important role in the induction of CI-PCD. In this review we report current knowledge on CI-PCD and provide evidence for its regulation by chemotherapeutic agents currently used in the clinic and under investigation in clinical trials. Lastly, we discuss how the study of natural and synthetic agents triggering CI-PCD may help in the pharmacological design of a new generation of more effective chemotherapeutic drugs. The use of such drugs activating both CD-PCD and CI-PCD pathways should achieve a more successful eradication of carcinogenic cells and the attainment of lower levels of tumor resistance.

Tactile resonance sensors in medicine.

Tactile sensors in general are used for measuring the physical parameters associated with contact between sensor and object. Tactile resonance sensors in particular are based on the principle of measuring the frequency shift, Deltaf, defined as the difference between a freely vibrating sensor resonance frequency and the resonance frequency measured when the sensor makes contact to an object. Deltaf is therefore related to the acoustic impedance of the object and can be used to characterize its material properties. In medicine, tactile resonance sensor systems have been developed for the detection of cancer, human ovum fertility, eye pressure and oedema. In 1992 a Japanese research group published a paper presenting a unique phase shift circuit to facilitate resonance measurements. In this review we summarize the current state-of-the-art of tactile resonance sensors in medicine based on the phase shift circuit and discuss the relevance of the measured parameters for clinical diagnosis. Future trends and applications enabled by this technology are also predicted.

Temporal correlations of local network losses.

We introduce a continuum model describing data losses in a single node of a packet-switched network (like the Internet) which preserves the discrete nature of the data loss process. By construction, the model has critical behavior with a sharp transition from exponentially small to finite losses with increasing data arrival rate. We show that such a model exhibits strong fluctuations in the loss rate at the critical point and non-Markovian power-law correlations in time, in spite of the Markovian character of the data arrival process. The continuum model allows for rather general incoming data packet distributions and can be naturally generalized to consider the buffer server idleness statistics.

Effects of protein phosphorylation on ubiquitination and stability of the translational inhibitor protein 4E-BP1.

The availability of the eukaryotic polypeptide chain initiation factor 4E (eIF4E) for protein synthesis is regulated by the 4E-binding proteins (4E-BPs), which act as inhibitors of cap-dependent mRNA translation. The ability of the 4E-BPs to sequester eIF4E is regulated by reversible phosphorylation at multiple sites. We show here that, in addition, 4E-BP1 is a substrate for polyubiquitination and that some forms of 4E-BP1 are simultaneously polyubiquitinated and phosphorylated. In Jurkat cells inhibition of proteasomal activity by MG132 enhances the level of hypophosphorylated, unmodified 4E-BP1 but only modestly increases the accumulation of high-molecular-weight, phosphorylated forms of 4E-BP1. In contrast, inhibition of protein phosphatase activity with calyculin A reduces the level of unmodified 4E-BP1 but strongly enhances the amount of phosphorylated, high-molecular-weight 4E-BP1. Turnover measurements in the presence of cycloheximide show that, whereas 4E-BP1 is normally a very stable protein, calyculin A decreases the apparent half-life of the normal-sized protein. Affinity chromatography on m(7)GTP-Sepharose indicates that the larger forms of 4E-BP1 bind very poorly to eIF4E. We suggest that the phosphorylation of 4E-BP1 may play a dual role in the regulation of protein synthesis, both reducing the affinity of 4E-BP1 for eIF4E and promoting the conversion of 4E-BP1 to alternative, polyubiquitinated forms.

Changes in levator ani anatomical configuration following physiotherapy in women with stress urinary incontinence.

PURPOSE: We quantified the effect of pelvic floor muscle training on the anatomical configuration of the levator ani using magnetic resonance imaging. MATERIALS AND METHODS: Five female participants with stress urinary incontinence underwent magnetic resonance imaging before and after participating in a pelvic floor muscle physiotherapy program. Axial T1-weighted images of the levator ani were taken with the participant in a supine position. Source images were then manually segmented and surface modeling was applied to build a 3-dimensional model of the levator ani. Models were then measured to determine the levator ani surface area as well as the encircled volume at rest and during voluntary contraction. The percentage of levator ani retraction and symphysis pubis movement during voluntary contraction before and after physiotherapy were also measured. RESULTS: After physiotherapy the levator ani surface area at rest was significantly smaller than before physiotherapy, decreasing from 677.11 +/- 45.00 to 620.48 +/- 36.14 mm(2) (p = 0.04). The relative reduction in volume encircled by the levator ani during contraction increased significantly from -11.66 +/- 7.42 to -26.02 +/- 13.52 mm(3) (p = 0.04). Levator ani surface retraction during a voluntary contraction increased significantly from 65.61% +/- 17.07% to 81.70% +/- 16.30% (p = 0.02). Symphysis pubis movement during pelvic floor muscle contraction decreased from 1.45 +/- 1.32 to 0.44 +/- 0.61 mm (p = 0.05). CONCLUSIONS: Findings from this preliminary study indicate that pelvic floor muscle training results in anatomical changes in the levator ani and reduction of pubic movement. These results provide insight into the possible anatomical mechanisms through which physiotherapy enables the pelvic floor muscle to minimize urine leakage.

Regulation of translation factors eIF4GI and 4E-BP1 during recovery of protein synthesis from inhibition by p53.

Activation of the tumour suppressor protein p53 rapidly inhibits protein synthesis. This is associated with dephosphorylation and cleavage of initiation factor eIF4GI and the eIF4E-binding protein 4E-BP1. When the activation of p53 is reversed within 16 h 4E-BP1 becomes rephosphorylated, the level of intact eIF4GI slowly increases and protein synthesis gradually recovers. The recovery of protein synthesis is partially blocked by rapamycin and wortmannin but not by the protein kinase inhibitors PD98059 and CGP74514A. Both rapamycin and wortmannin, but not PD98059 or CGP74514A, delay the reappearance of eIF4GI. In contrast, full-length 4E-BP1 rapidly becomes rephosphorylated and this process is partially inhibited by rapamycin, PD98059 and CGP74514A. Thus, activation of p53 results in the inhibition of distinct rapamycin- and wortmannin-sensitive pathways that target eIF4GI, and rapamycin-sensitive and -insensitive pathways that target 4E-BP1. Following inactivation of p53 the gradual recovery is determined largely by the kinetics of restoration of eIF4GI rather than by the rephosphorylation of full-length 4E-BP1. These findings suggest that the ability of cells to rephosphorylate 4E-BP1, resynthesise eIF4GI and restore the rate of protein synthesis after inactivation of p53 is an important aspect of recovery following the relief of physiological stress.

Random walks in local dynamics of network losses.

We suggest a model for data losses in a single node (memory buffer) of a packet-switched network (like the Internet) which reduces to one-dimensional discrete random walks with unusual boundary conditions. By construction, the model has critical behavior with a sharp transition from exponentially small to finite losses with increasing data arrival rate. We show that for a finite-capacity buffer at the critical point the loss rate exhibits strong fluctuations and non-Markovian power-law correlations in time, in spite of the Markovian character of the data arrival process.

Effects of artificial obstruction on the function of the upper urinary tract of Guinea pigs, rats and pigs.

PURPOSE: Four different experiments in animals were performed to evaluate the influence of pyelo-ureteral surgery on the function of the upper urinary tract. METHODS: Experiment I: In 17 female guinea pigs pyelo-ureteral anastomosis was performed microsurgically. Three months later, the ureteral peristalsis was investigated by measuring the intraureteral pressure and the in vitro activity of the renal pelvic and ureteric wall was analysed. Experiment II: 10 rats were used for microsurgical uretero-ureteral anastomosis. One month after surgery the pyelo-ureteral peristalsis was examined by videomicroscopy while simultaneously measuring the renal pelvic and intravesical pressure. Subsequently the kidneys were removed for histological examination. Experiment III: In 2 pigs unilateral pyeloplasty was performed. Using an implanted transmitter the intravesical and the renal pelvic pressures were recorded continuously over a time interval of 3 months. Five months after surgery the pyelo-ureteral peristalsis was investigated by pyelography. The kidneys were then removed for histological and biomechanical examinations. Experiment IV: A partial artificial obstruction was performed in 16 guinea pigs by implanting the ureter into the psoas muscle. Two to six months following surgery their upper urinary tracts were removed for analysis of in vitro activity as well as histological and immunohistochemical investigations of the ureter and renal pelvis. RESULTS: Experiment I: Ultrasound investigation showed in all cases a significant dilation of the renal pelvis. The ureteral contraction frequency distally was decreased in vivo as well as in vitro (p <0.05) compared with the controls. Experiment II: Videomicroscopic imaging showed in eight out of nine cases an interruption of the peristaltic wave below the anastomosis; the ureteral peristalsis was restored distally by ureteral contractions with a decreased frequency. Retroperistalsis was seen in the lower part of the ureter. The frequency of renal pelvic and ureteral contractions were decreased (p <0.05). Renal pelvic baseline pressure as well as contraction amplitude were irregularly changed. Histological examinations showed increased connective tissue within the renal pelvic wall in all cases. Experiment III: In both pigs an intermittent change in contraction frequency of the renal pelvis was found, associated with a changing contraction amplitude. Five months after surgery an interruption of the peristaltic wave was detected in both pigs. Histological examinations showed increased connective tissue within the renal pelvic wall. The stiffness of caliceal and pelvic tissue was lower following the pyeloplasty compared to the controls. Experiment IV: Following artificial partial ureteral obstruction in all guinea pigs the in vitro investigations showed an increased spontaneous activity of the upper urinary tract except in the proximal part of the ureter. Ureteral obstruction produced a change in contraction pattern of the proximal ureter and a decrease in contraction frequency of the distal ureter. Immunohistochemical investigations revealed rarefication and disorientation of nerve fibres within the proximal ureteric wall. CONCLUSIONS: Surgical interruption of the ureteral continuity and re-anastomosis cause a temporary disruption of the peristaltic wave at the anastomosis site. Ureteral peristalsis is restored by ureteral contractions associated with retroperistalsis as well as a decreased contraction frequency. Uretero-ureteral anastomosis in rats, pyelo-ureteral anastomosis in guinea pigs and pyeloplasty in pigs seem to influence the upper urinary tract similarly to a chronical functional obstruction, causing changes in pyelo-ureteral motility and spontaneous muscular activity of the renal pelvic and ureteral wall as well as biomechanical and histological characteristics.

Determining the displacement of the pelvic floor and pelvic organs during voluntary contractions using magnetic resonance imaging in younger and older women.

OBJECTIVES: To: (i) visualize the effect of sustained voluntary contractions on the anatomical configuration of the pelvic floor (PF) muscles using magnetic resonance imaging (MRI); (ii) examine the effect of ageing on the range of displacement of the PF contents secondary to contraction and simulating incontinence exercises; and (iii) introduce the concept of contractile change in volume (DeltaPF-V) using three-dimensional (3D) reconstruction from axial, sagittal and coronal MRI. SUBJECTS AND METHODS: Two groups of continent women volunteers, familiar with correct PF contraction, were evaluated. The mean (sd) age in group I was 34 (6) years and that of group II 55 (9) years; the mean parities were 0.7 and 2.2, respectively. MRI was conducted with the women supine and data were obtained in the axial, sagittal and coronal planes. In each plane, images were obtained with the PF relaxed and subsequently with the PF contracted over 10-20 s. Image processing was used to enhance the anatomical boundaries of the pelvic organs and to measure the displacement produced by the contraction. Displacements, observed between each image pair, were colour-coded to highlight the geometric differences between a relaxed and contracted PF and to facilitate measuring displacement. Data measured from each group were pooled and the range of motion expressed as the mean (sd), compared using Student's t-test. RESULTS: Digitally processed imaging allowed an accurate comparison between the relaxed and contracted PF, and highlighted the differences between them. From these views, the levator ani displaced the vagina asymmetrically in nine of the 11 older subjects, and in six of the 17 younger subjects. The values from the imaging in the sagittal and coronal plane for the two groups were: levator ani displacement, 7.4 (1.1) and 1.4 (0.2) cm (P < 0.002), superior bladder wall, 4.2 (0.5) and 1.0 (0.1) cm (P < 0.002). There were also significant differences in the range of displacement produced by voluntary PF contraction in the internal structures; external outlines did not reflect these changes. The maximum displacement of the gluteal surface in the coronal plane did not change significantly; in group I it was 3.9 (1.8) to 2.9 (0.7) cm. From the 3D re-construction, DeltaPF-V for the younger women was significantly larger, at 23.3 (3.9) mL (P < 0.01) than in the older women, at 9.1 (4.4) mL. CONCLUCION: The range of motion over which voluntary PF contractions displace the bladder and vagina is age-dependent, being higher in younger than in older subjects. It remains to be established whether range of movement is a limitation caused by neuronal factors, decrease in muscle strength/mass, or the substitution of spaces with fat (restricting free movement), or other factors.

Influence of gender on the diurnal variation of urine production and micturition characteristics of the rat.

The diurnal variation in the frequency/volume characteristics of male and female conscious rats was evaluated with reference to fluid consumption and urine production. Baseline values of the micturition volume and frequency of nine male and 10 female SD adult rats were measured over a 24-hour time period. The level of initial hydration conditions was standardized with 5 ml of water administered orally. With animals in a metabolism chamber having free access to water, the total volume of water consumed, the frequency/volume characteristics during micturition and the urine production rate were derived from the measurements of voided volume as detected by a digital balance. To establish reliability of measurements two separate micturition studies were done per rat at an interval of 1 week. Mean frequency of micturition and mean volume voided per micturition and urine production rate were computed in 3-hour time bins and represented over the 24-hour period. In addition the mean values of the number of micturitions and mean micturated volumes during the day/dark cycle were evaluated. The results show significant gender specificity in water consumption, urine production, and diurnal variations in micturition frequency/volume characteristics. Females consistently consume significantly larger amounts of water (83%) than males while urine production rate was correspondingly higher in females. It is concluded that water consumption and urine production are gender-specific. Because higher volumes of water are imbibed by females than males, the frequency/volume characteristic of micturition in the rat is also gender-specific. Data suggest that the volume voided per micturition depends on the urine production rate.

Gender specificity of tolterodine on micturition and the diurnal variation of urine production of the conscious rat.

OBJECTIVE: To evaluate the effect of the oral administration of tolterodine on the diurnal micturition characteristics of the male and female conscious rat, and to examine the relative effect of tolterodine in influencing water consumption and urine production. MATERIALS AND METHODS: Baseline micturition volume and frequency characteristics of nine male and 10 female Sprague-Dawley age-matched adult rats (body weight 399 +/- 15 and 249 +/- 3 g, respectively) were evaluated over 24-h. Initial hydration conditions were standardized with an oral dose (5 mL) of water. Rats were subsequently placed in a metabolic cage and had free access to water. Micturition volume/frequency characteristics were derived from the measurements of voided volume (measured using a digital balance below the metabolic cage and connected to a computer). The total volume of water consumed over the 24 h was also measured. Two separate baseline studies were conducted, followed by the administration of a single oral dose of 1 mg/mL of tolterodine dissolved in 5 mL of water. The mean frequency of micturition and mean volume voided per micturition were computed in 3-h periods and plotted over the 24-h period. In addition, the mean values of the number of micturitions and voided volumes during the day/dark cycle were evaluated. RESULTS: Baseline data showed that females (when corrected for body weight) consistently imbibed significantly more water (83%) than did male rats. Tolterodine did not significantly affect water consumption in the males but significantly reduced water consumption in females by 42%. Tolterodine did not significantly affect the amount of urine produced by male rats but significantly reduced the total amount of urine production in females by 26%. Tolterodine significantly increased the number of voids in male rats compared with baseline during the day but not during the night. More importantly tolterodine produce no significant effect on the volume voided per micturition in male rats either during the day or night cycle, but significantly decreased the volume voided per micturition in females. CONCLUSIONS: These results suggest that the effect of tolterodine on micturition is gender-specific, suppressing water consumption and urine production in female but not male rats, and decreasing bladder volume. There is a possibility that the reported clinical effects of tolterodine arise through the suppression of fluid consumption.

Functional evaluation of Tadenan on micturition and experimental prostate growth induced with exogenous dihydrotestosterone.

OBJECTIVES: To evaluate the effect of Tadenan (TAD; Pygeum africanum extract) pretreatment on the micturition characteristics of conscious and anesthetized rats consequent to dihydrotestosterone (DHT) administration and to examine the influence of such treatment on the growth of the prostate. METHODS: Studies using 40 adult Sprague-Dawley male rats were performed during a 7-week period. These animals were treated with DHT 1.25 mg/kg subcutaneously dissolved in peanut oil and/or TAD 100 mg/kg orally dissolved in sesame oil, except for the controls, which received vehicle only. Rats were divided into four groups: group 1 (control), vehicle only; group 2, DHT administered during weeks 3 and 4; group 3, TAD pretreatment, administered during weeks 1 and 2, followed by the combined administration of DHT and TAD during weeks 3 and 4 and TAD only during weeks 5 to 7; and group 4, continuous TAD treatment for 7 weeks. Micturition of conscious rats was evaluated in metabolic chambers, and in anesthetized rats, cystometrograms were done at the end of 7 weeks. RESULTS: DHT or DHT plus TAD did not produce significant changes in the volume but did reduce the frequency of micturition. TAD given alone significantly increased the volume of micturition and the rate of urine production. Cystometrographic studies in anesthetized rats revealed that DHT produced micturition characteristics similar to obstruction. The DHT plus TAD and TAD pretreatment data showed no significant difference from controls, suggesting that in the presence of TAD, the effects of DHT were negated. The total prostate weight of DHT and DHT plus TAD pretreated rats increased, and in the TAD group, these values decreased to lower than controls; growth of the ventral lobes was suppressed in the presence of TAD. CONCLUSIONS: These results demonstrate that TAD pretreatment significantly reduces the "obstructive" effects of DHT on micturition, counteracts the hormone-induced enlargement of the prostate, and reduces prostate weight in the ventral but not the dorsal lobe.

A comparison of outbreak- and nonoutbreak-related multidrug-resistant tuberculosis among human immunodeficiency virus-infected patients in a South African hospital.

Nosocomial multidrug-resistant tuberculosis (MDR-TB) in human immunodeficiency virus (HIV)-infected people is recognized in Europe and America. We report the first such outbreak in South Africa. Six hospitalized women, identified by DNA fingerprinting, were infected with an outbreak strain of MDR-TB while receiving treatment for drug-susceptible tuberculosis. The putative source case was identified as an HIV-positive woman who underwent prolonged hospitalization for chronic cavitary tuberculosis. Compared with other HIV-positive patients in the hospital, outbreak patients were more immunocompromised, had fewer cavitary lung changes, and were less likely to have been treated before. They had high fevers, infiltrative patterns on chest radiographs, and a mean survival of 43 days. When individual isolation is not possible, separating highly immunocompromised patients with first-time tuberculosis from previously treated patients with cavitary lesions and from those with established drug resistance may reduce nosocomial transmission.

Age dependent response to exogenous estrogen on micturition, contractility and cholinergic receptors of the rat bladder.

The age related effects of 17beta-estradiol (E) supplementation on micturition and contractility of ovariectomized rats (OVX) were evaluated. Studies were carried out in young, 2 month, and mature, 10 month old rats which were distributed into three groups: Sham-operated (SHAM), (OVX), and (OVX+E). Following treatment, urodynamic studies were performed followed by an in vitro bladder tissue evaluation. Urodynamic studies show age and time related changes in bladder function. The in vitro results show that the hormone deprived tissues of 2 months old rats had a decreased responsiveness to cholinergic stimulation; maximum contractile force occurred at 78% and 187% for the SHAM. The response from the OVX+E tissues was evident at 113%. E supplementation of the mature rats increased bladder contractile force to the same levels as SHAM (156% and 176%). The response of the mature OVX rats remained significantly below that of SHAM or OVX+E rats. Findings suggest that the impact of E on bladder function depends on age at which it is given. Differential response between young and mature to exogenous E indicates that endogenous estrogen plays a major role in the neuromuscular development of normal bladder function and micturition reflexes. Contractility data show that OVX in young rats irreversibly decreases the response of the bladder to cholinergic stimulation, suggesting that exogenous E partially restores function while in mature rats, exogenous E was able to reverse the effects of OVX.