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A high-molecular-weight nondialysable material (NDM) isolated from cranberry juice at a concentration of 0.6 to 2.5 mg/ml dissociated coaggregates formed by many intergeneric oral bacteria. A lower concentration of NDM was required to inhibit formation of such coaggregates. NDM acted preferentially on pairs of oral bacteria in which one or both members are Gram-negative anaerobes. The high-molecular-weight material from blueberry also inhibited the coaggregation, although its activity was weaker, whereas such materials obtained from other fruits were inactive. Saliva did not interfere with the ability of NDM to inhibit coaggregation. A preliminary clinical trial showed that NDM reduces S. mutans counts in saliva. The antiadhesion activity of cranberry juice has a potential for altering the oral microbial flora resulting in improved oral hygiene.

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During the early stages of budding, cell wall remodeling and polarized secretion are concentrated at the bud tip (apical growth). The CBK1 gene, encoding a putative serine/threonine protein kinase, was identified in a screen designed to isolate mutations that affect apical growth. Analysis of cbk1Delta cells reveals that Cbk1p is required for efficient apical growth, proper mating projection morphology, bipolar bud site selection in diploid cells, and cell separation. Epitope-tagged Cbk1p localizes to both sides of the bud neck in late anaphase, just prior to cell separation. CBK1 and another gene, HYM1, were previously identified in a screen for genes involved in transcriptional repression and proposed to function in the same pathway. Deletion of HYM1 causes phenotypes similar to those observed in cbk1Delta cells and disrupts the bud neck localization of Cbk1p. Whole-genome transcriptional analysis of cbk1Delta suggests that the kinase regulates the expression of a number of genes with cell wall-related functions, including two genes required for efficient cell separation: the chitinase-encoding gene CTS1 and the glucanase-encoding gene SCW11. The Ace2p transcription factor is required for expression of CTS1 and has been shown to physically interact with Cbk1p. Analysis of ace2Delta cells reveals that Ace2p is required for cell separation but not for polarized growth. Our results suggest that Cbk1p and Hym1p function to regulate two distinct cell morphogenesis pathways: an ACE2-independent pathway that is required for efficient apical growth and mating projection formation and an ACE2-dependent pathway that is required for efficient cell separation following cytokinesis. Cbk1p is most closely related to the Neurospora crassa Cot-1; Schizosaccharomyces pombe Orb6; Caenorhabditis elegans, Drosophila, and human Ndr; and Drosophila and mammalian WARTS/LATS kinases. Many Cbk1-related kinases have been shown to regulate cellular morphology.

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To determine the effects of creatine supplementation on cardiorespiratory responses during a graded exercise test (GXT) 36 trained adults (20 male, 16 female; 21-27 years old) performed two maximal GXTs on a cycle ergometer. The first GXT was done in a nonsupplemented condition, and the second GXT was done following 7 days of ingesting either 5 g creatine monohydrate, encased in gelatin capsules, four times daily (CS, 13 male, 6 female), or the same number of glucose capsules (PL, 7 male, 10 female). CS significantly (P<0.05) improved total test time [pre-CS = 1217 (240) s, mean (std. dev.) versus post-CS = 1289 (215) s], while PL administration had no effect (P>0.05) on total test time [pre-PL= 1037 (181) s. versus post-PL= 1047 (172) s]. In addition, both oxygen consumption (VO2) and heart rate at the end of each of the first five GXT stages were significantly lower after CS, but were unchanged after PL. Moreover, the ventilatory threshold occurred at a significantly greater VO2 for CS [pre-CS = 2.2 (0.4) l x min(-1) or 66% of peak VO2 versus post-CS = 2.6 (0.5) l x min(-1) or 78% of peak Vo2; pre-PL = 2.6 (0.9) l x min(-1) or 70% peak VO2 versus post-PL = 2.6 (1.1) l x min(-1) or 68% of peak Vo2]. Neither CS nor PL had an effect on peak Vo2 [pre-CS = 3.4 (0.7) l x min(-1) versus post-CS = 3.3 (0.7) l x min(-1); pre-PL = 3.7 (1.1) l x min(-1) versus post-PL = 3.7 (1.1) l x min(-1)]. Apparently, CS can alter the contributions of the different metabolic systems during the initial stages of a GXT. Thus, the body is able to perform the sub-maximal workloads at a lower oxygen cost with a concomitant reduction in the work performed by the cardiovascular system.

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OBJECTIVE: Thermal sensation and the physiological responses of women (follicular phase) exposed to 17 degrees C immersion for 120 minutes were investigated. METHODS: The subjects were divided into 2 groups by percent body fat (low fat [LF] = 21% +/- 2% [mean +/- SD] vs high fat [HF] = 30% +/- 3%). A 2-way analysis of variance was used to determine differences between the groups in metabolism, metabolism derived from carbohydrate, metabolism derived from fat, blood glucose, rectal temperature, skin temperature, and thermal sensation. RESULTS: As anticipated, pooled metabolism increased across the 120-minute immersion. Metabolism derived from carbohydrate was significantly higher in the LF than in the HF group and increased across time. Blood glucose decreased significantly across time, yet there was no group difference, suggesting that the LF group may have utilized a greater proportion of intramuscular glycogen. The HF group demonstrated a higher rectal temperature compared to their LF counterparts. Overall, rectal temperature demonstrated a group x time interaction as immersion continued. However, rectal temperature for all subjects remained above 35 degrees C. Surprisingly, the HF group perceived significantly greater thermal discomfort than did their LF counterparts. CONCLUSIONS: Since intramuscular glycogen utilization is associated with shivering thermogenesis, the suspected greater utilization of this fuel by the LF group may have contributed to less thermal discomfort than in the HF group. However, since glycogen utilization was not directly measured, this speculation cannot be validated. It is also possible that the modified thermal sensation scale we used may not be an adequate marker of thermal discomfort in females with a high percentage of body fat (28% to 35%) exposed to cold water immersion.

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The p21-activated kinases (PAKs) are effectors for the Rho-family GTPase Cdc42p. Here we define the in vivo function of the kinase activity of the budding yeast PAK Cla4p, using cla4 alleles that are specifically inhibited by a cell-permeable compound that does not inhibit the wild-type kinase. CLA4 kinase inhibition in cells lacking the partially redundant PAK Ste20p causes reversible SWE1-dependent cell-cycle arrest and gives rise to narrow, highly elongated buds in which both actin and septin are tightly polarized to bud tips. Inhibition of Cla4p does not prevent polarization of F-actin, and cytokinesis is blocked only in cells that have not formed a bud before inhibitor treatment; cell polarization and bud emergence are not affected by Cla4p inhibition. Although localization of septin to bud necks is restored in swe1Delta cells, cytokinesis remains defective. Inhibition of Cla4p activity in swe1Delta cells causes a delay of bud emergence after cell polarization, indicating that this checkpoint may mediate an adaptive response that is capable of promoting budding when Cla4p function is reduced. Our data indicate that CLA4 PAK activity is required at an early stage of budding, after actin polarization and coincident with formation of the septin ring, for early bud morphogenesis and assembly of a cytokinesis site.

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This investigation evaluated the influence of gender and phase of menstrual cycle [follicular (FOL): Days 2-6) and luteal (LUT: Days 19-24)] on a cold air tolerance test (CATT: 90-min of exposure to 5 degrees C air) in 8 females (22.7 +/- 3.0 yr) and 15 males (22.3 +/- 2.9 yr). In addition, central thermosensitivity (beta; W x kg(-1) x degrees C(-1) [i.e., the slope of the relationship between the decrease in esophageal temperature (Tes) and the increase in heat production (HP)], gathered during a separate water trial in 20 degrees C water, was correlated to the change (delta) in Tes and HP across the 90 min of resting exposure during the CATT. Analysis of variance revealed no significant differences between phase of menstrual cycle or gender for HP, mean skin temperature (Tsk), and insulation; however, a main effect for time for these parameters was demonstrated. Despite these similarities, Tes differed (P < 0.05) between males and females. Additionally, no relationship was found between beta and deltaHP and deltaTes in the males and females. Also, there was no relationship between beta and thermoregulation during the CATT in these subjects. These data suggest that menstrual cycle phase did not cause a differential response in Tes, Tsk, and HP during a CATT. Furthermore, women maintained a higher Tes than men during the CATT despite similarities in HP and Tsk.

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BACKGROUND: This investigation evaluated the influence of gender and phase of menstrual cycle [follicular (FOL: days 2-6) and luteal (LUT: days 19-24) phases] on thermosensitivity and metabolic heat production (HP) during cold water immersion (20 degrees C) in 10 females (22.4 +/- 2.8 yr) and 16 males (22.4 +/- 2.9 yr). METHODS: Following a 20-min baseline period (BASE), subjects were immersed until esophageal temperature (Tes) reached 36.5 degrees C or for a maximum pre-occlusion (Pre-OCC) time of 40 min. An arm and thigh cuff were then inflated to 180 and 220 mmHg, respectively, for 10 min (OCC). Following release of the inflated cuffs (Post-OCC), the slope (beta) of the relationship between the decrease in Tes and the increase in HP was used to quantify thermosensitivity. RESULTS: ANOVA revealed no significant difference in thermosensitivity between phases of the menstrual cycle or between men and women (FOL = -2.76, LUT = -3.05, Males = -3.24 W x kg(-1) x degrees C(-1)). A significant (p < 0.05) main effect for gender for HP, and a significant (p < 0.05) main effect for menstrual phase for mean skin temperature (Tsk) were observed. CONCLUSIONS: These data suggest, despite gender differences in HP, that the thermosensitivity of HP during cold water immersion is similar between males and females and is not influenced by menstrual cycle phase. Therefore, these data indicate that when faced with a cold challenge, women respond similarly to men in both phases of their menstrual cycle.

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Recent studies suggest that histamine H2-receptor antagonists may be useful in the treatment of urticaria. This study was conducted to determine whether famotidine, a H2 antagonist, is effective in the treatment of acute urticaria and compare its effect with that of the H1 antagonist diphenhydramine. In this prospective, double-blind, controlled trial, 25 patients with urticaria of less than 72 h duration were randomized to receive a single dose of either famotidine 20 mg i.m. or diphenhydramine 50 mg i.m. Prior to treatment and 30 min after treatment, patients rated pruritus and sedation using visual analogue scales, while physicians evaluated intensity of urticaria and percentage of body surface area involved by urticaria. Famotidine was found to reduce pruritus associated with acute urticaria, intensity of urticaria, and body surface area affected by urticaria without causing sedation. Famotidine was comparable to diphenhydramine in efficacy; however, there was a (nonsignificant) trend for diphenhydramine to be more effective than famotidine in the treatment of pruritus, and for famotidine to be more effective in the reduction of surface area of involvement. It is concluded that famotidine merits further investigation as a potential medication for treatment of urticaria.

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PURPOSE: To determine the effect on iris color of discontinuing latanoprost (LP) treatment in a patient with pronounced iris color darkening, and to assess the possible role of sympathetic innervation. METHODS: In a patient demonstrating pronounced iris color darkening in both eyes after treatment with LP for 6 months, magnified iris color photographs were taken at 3- to 6-month intervals for 5 years after discontinuation of LP treatment. Pupillary testing for sympathetic insufficiency was performed with cocaine 10% or hydroxyamphetamine 1%. RESULTS: The iris color did not appreciably change after discontinuing LP. The cocaine-induced increase in pupillary diameter was considerably greater for the control subject than for the patient who demonstrated the LP-induced color change. CONCLUSIONS: Latanoprost-induced iris color darkening does not appreciably change for several years after discontinuing treatment. Some eyes that show LP-induced darkening may have relative ocular sympathetic insufficiency.

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BACKGROUND: Despite the efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of obsessive-compulsive disorder, a significant number of patients show no or only partial remission of symptoms. Some evidence exists to suggest that risperidone augmentation can be helpful in treating this refractory group. The efficacy of other atypical antipsychotic agents, such as olanzapine, in augmenting SSRIs in refractory obsessive-compulsive patients has yet to be systematically investigated. METHOD: A series of 10 patients with DSM-IV obsessive-compulsive disorder showing significant residual symptoms following an adequate SSRI trial (12 weeks) were given open-label olanzapine augmentation for a minimum of an additional 8 weeks. Treatment response was assessed using the Yale-Brown Obsessive Compulsive Scale and the Clinical Global Impressions scale. RESULTS: Nine of the 10 patients in this series treated with olanzapine and an SSRI completed the 8-week augmentation trial. Of these, 4 demonstrated a complete remission or major improvement in obsessive-compulsive symptoms, 3 had partial remission, and 2 experienced no benefit. Nine patients experienced minimal adverse effects, primarily sedation, which did not interfere with continuing treatment. One patient discontinued olanzapine owing to excessive sedation. CONCLUSION: The results of this preliminary, open-label trial suggest that olanzapine may be effective in augmenting ongoing SSRI treatment for a portion of patients with obsessive-compulsive disorder refractory to SSRI treatment. Larger, placebo-controlled trials appear warranted to investigate the clinical efficacy and tolerability of olanzapine augmentation of SSRI treatment in SSRI-refractory obsessive-compulsive disorder.

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BACKGROUND: At rest during cold exposure, the amount of body fat plays an important role in the maintenance of core temperature. High fat (HF) individuals would therefore have an advantage as compared with their low fat (LF) counterparts. Since females usually have a higher amount of body fat than males they are expected to maintain core temperature at a lower energy cost. METHODS: The purpose of the present investigation was to dichotomize female subjects by percent fat (LF = 20.5 +/- 2%, n = 6 vs. HF = 30 +/- 3%, n = 6) to elucidate the thermal and metabolic responses during acute exposure to 17 degrees C water for 120 min. The following variables were measured: rectal temperature (Tre; degrees C), mean skin temperature (Tsk; degrees C), oxygen consumption (VO2; ml x kg(-1) x min(-1)), and tissue insulation (I; degrees C x m2 x W(-1)). The experiment-wise error rate was set a priori at p = 0.05. RESULTS: Unexpectedly, only one of the variables demonstrated a main effect for fat (p < 0.05). Tre demonstrated a significant (p < 0.05) group by time interaction. However, Tsk and I demonstrated a main effect for time (p < 0.05). While VO2 demonstrated an increase across time, these changes were non-significant (p > 0.05). It appears that the HF group demonstrated a similar thermal (I and Tsk) and metabolic (VO2) response as compared with the LF counterparts. However, the LF groups maintained a lower Tre as compared with the HF subjects. Perhaps leaner subjects or colder water temperatures would elucidate the value of body fat in females, and demonstrate a differential response with respect to females varying in percent body fat.

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OBJECTIVE: Depression is twice as common in women as in men, but the reason for this sexual dimorphism is unknown. This article reviews recent studies of the role of childhood sexual abuse in the subsequent development of major depressive disorder, and the biological and psychosocial mechanisms by which early stressors may contribute to adult-onset depression in women. Particular attention is paid to investigations of the long-term effects of early stress on hypothalamic-pituitary-adrenal (HPA) axis function. METHOD: Studies were identified by means of computerized and manual searches; further references were obtained from the bibliographies of reviewed articles. RESULTS: Childhood sexual abuse is associated with adult-onset depression in both men and women, and occurrence of such abuse is more common in girls than in boys. There is evidence from both animal and human studies that early stressors produce long-term dysregulation of the HPA axis similar to that seen in depressed patients and that such dysregulation results in a differential response to stressors in adulthood. In addition, it appears that the HPA axis in females may be more susceptible to stress-induced dysregulation, which might contribute to an increased vulnerability to depression in adulthood. CONCLUSIONS: Childhood sexual abuse is an important early stressor that may predispose individuals to adult-onset depression by means of dysregulation of the HPA axis. Investigation of the mechanisms mediating the relationship between childhood sexual abuse and adult-onset depression, and the study of gender differences in exposure to this and other stressors, may improve our understanding of the etiology of depressive illness in general.

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BACKGROUND: Men with high fat body composition maintain higher core temperatures, and lower aerobic metabolic rates than their low fat counterparts thus, verifying the insulatory benefit of body fat. Females, on average have more body fat and less muscle mass than males, and may maintain rectal temperature (Tre) at a lower energy cost. METHODS: The present investigation dichotomized female subjects by percent fat (low fat; n = 3, LF = 19.2+/-3% vs. high fat; n = 4 HF: 29.9+/-3%) to elucidate the thermal and metabolic responses during acute exposure to 5 and 27 degrees C air for 120 min. An ANOVA was used to examine the following: Tre (degrees C), mean skin temperature (Tsk; degrees C), oxygen consumption (VO2; ml x kg(-1) x min(-1)) and tissue insulation (I; degrees C x m2 x W(-1)). For Tre, a significant fat x time interaction (p < 0.05) was demonstrated at both 5 and 27 degrees C, whereby Tre tended to be lower in the LF group than the HF group. VO2 at 5 degrees C demonstrated a main effect for time only. For I, a main effect for time was noted at 5 degrees C. Also for I, a trend (p = 0.06) toward a main effect of fat during exposure to 5 degrees C was noted while at 27 degrees C a main effect (p < 0.05) was demonstrated. RESULTS: From this data it appears that under these conditions, the HF group demonstrated higher Tre and I values than their LF counterparts that was not accompanied with a differential response with respect to aerobic metabolic rate. Thus, the impact of body composition on energy expenditure to maintain Tre differs between LF and HF males and females.

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BACKGROUND: Capsaicin alters thermoregulation in adult rats by producing a dose-dependent fall in body temperature and metabolism. The present investigation examined the thermal and metabolic responses in males who were fed capsaicin (CAP: 2 mg.kg(-1) body weight) vs. a placebo (PL: a maltodextrin capsule) prior to immersion in cold water. METHODS: Seven Caucasian males aged 20-28 yr were immersed in 22 degrees C twice (PL vs. CAP), for 120 min. The following were examined: metabolism (M; W.m(-2)), rectal temperature (Tre; degrees C), mean skin temperature (Tsk; degrees C), tissue insulation (I; degrees C.m(-2).W(-1) and proportion of energy derived from carbohydrate (%CHO). RESULTS: For M, Tre, I, and Tsk there was no significant differences between treatments (PL vs. CAP) when the variables were pooled jointly over time. However, significant differences across time was detected for Tre (p = 0.0003), Tsk (p = 0.0147), and M (p = 0.0036). Values for %CHO demonstrate a main effect for treatment (p = 0.0210) suggesting the CAP (46.7-/+25.9%) treatment demonstrated a decreased reliance on carbohydrate utilization for energy provision as compared to the PL (75.0+/-21.9%) treatment. Additionally, the treatment x time interaction was significant (p = 0.0096) whereby, PL differed from CAP at 5 min only. CONCLUSION: From these data it appears that while M, Tre, and Tsk differed across time, a CAP (which differentially affected percent of energy derived from carbohydrate) feeding did not differentially affect the thermal and metabolic responses of males during acute cold water immersion.

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For patient populations whose heart rates cannot be used to regulate exercise intensity, the Borg Rating of Perceived Exertion (RPE) Scale is the preferred way to prescribe exercise intensity. Individual perceptual variations are best quantified by measuring perceptual intensity during maximal exercise testing; however, many situations require a submaximal protocol. Here, a submaximal treadmill procedure for establishing individualized target Ratings of Perceived Exertion is described. Target ratings of exertion were developed for outpatient cardiac rehabilitation patients using the new method and compared to target Ratings of Perceived Exertion obtained using standard techniques. A total of 144 target ratings at intensities ranging from 50% to 85% VO2max were compared. Over-all, the average difference between the two methods was 0.27 units and was not significant at any intensity. Therefore, the Treadmill Slope Method appears to be a valid submaximal test for generating target Ratings of Perceived Exertion for outpatient cardiac rehabilitation patients.

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The present investigation dichotomized female subjects by percentage of fat (low fat [LF] = 19.2+/-3% [n = 4] vs high fat [HF] = 29.9+/-3% [n = 4]) to elucidate the perceptual and physiological responses during acute exposure to 5 degrees C air for 120 min. Correlational analyses were used to assess the relationship between thermal sensection (TS) and differences between LF and HF groups. Significant (p < 0.01) differences existed between the groups for TS when values were pooled over time, where HF had a lower TS (5.9+/-0.6) than LF (7.9+/-0.5). Additionally, a significant (p < 0.01) main effect for time existed, where TS, when pooled over groups T5 (3.8+/-0.7) and T30 (5.4+/-0.9), was less than T60 (7.4+/-0.6), T90 (8.6+/-0.5), and T120 (9.1+/-0.4). No significant fat x time interaction was noted despite apparent perceptual differences between the groups at most of the time points. Further, the relationships between TS and percentage of fat and fat mass were either significant or exhibited strong trends toward significance at time points T5, T30, and T60. When rectal temperature (Tre) was pooled over the four time points, the fat groups differed significantly (p < 0.05); LF (-0.21+/-0.04 degrees C) exhibited a greater ATre than HF (-0.03+/-0.04 degrees C). When Tre was pooled across the fat groups, significant (p < 0.01) differences over time were detected. From these data, it appears that the modified TS scale tested may be a good marker of thermal discomfort in females exposed to the cold because perceptual differences were noted between the groups, accompanied by apparent differences in Tre between the LF and HF groups.

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