Biobehavioral treatment of excessive micturition

Five patients with excessive frequency of micturition were provided with a behavioral therapy — biofeedback treatment. The patients, three females, 22, 27, and 37 years of age, reported symptoms of dyspareunia and excessive frequency for 2–4 years; the two males included a 51-year-old who reported excessive frequency and pain in the bladder region for four years, and a 36-year-old who reported excessive frequency for 24 years. All of the patients had undergone traditional evaluations and treatments by urologists, yet their symptoms persisted although no organic pathology could be detected. Record-keeping data over a 4-week pre-treatment baseline indicated an average daily frequency of voiding of 15.7; the pain in the region of the bladder reported by three patients was an average of 5.2/day on a scale of 0–10.The treatment consisted of 3 phases throughout which all patients recorded: time of urinary urge, time of urination, and level of tension. The phases included: (1) four-week baseline; (2) biofeedback-assisted relaxation training at home using portable skin resistance trainers; (3) self-control using relaxation to gradually increase the delay between the time of the urge to urinate and the actual urination; and (4) follow-up, during which time the record-keeping was continued. An average of 11.4 sessions were required until the patients reported normal voiding frequency (average of 8.6/day) and absence of pain. Follow-up data ranging from 4 to 36 months indicated normal frequency was maintained in four of the five patients. The remaining female maintained the gains for five months, but then reverted to her baseline level at eight months.     

A radical view of pathological vasculature

Striking results reported by Okuno et?al. (2012) in the July issue of Nature Medicine show that the ataxia telangiectasia mutated (ATM) kinase counteracts excessive oxygen radical production in immature angiogenic blood vessels. Its deletion results in activation of the mitogen-activated protein kinase p38α and arrest?of pathological angiogenesis.     

The SK channel as a novel target for treating alcohol use disorders

We recently described the SK-type potassium channel as a novel target for treatment of excessive alcohol intake.1 SK channel function is reduced in the nucleus accumbens (NAcb) core in rats consuming alcohol under intermittent (IAA) but not continuous (CAA) access, and the FDA-approved SK activator chlorzoxazone reduces the excessive alcohol intake in IAA rats but not the more moderate intake in CAA rats. Here, we discuss the implications of these and related findings for SK as a treatment for alcohol use disorders. In addition, we report that many NAcb core electrophysiological parameters related to action potential waveform or basal parameters were not altered in alcohol-drinking rats. These results are in strong contrast to those reported for cocaine, where several NAcb ion channels show adaptations after cocaine exposure. These results suggest that alcohol intake is associated with only limited ion channel neuro-adaptations in the NAcb relative to cocaine, and support the hypothesis that SK represents a selective and potent intervention to reduce excessive alcohol intake.     

H2S Attenuates Sleep Deprivation-Induced Cognitive Impairment by Reducing Excessive Autophagy via Hippocampal Sirt-1 in WISTAR RATS

Sleep deprivation (SD) is widespread in society causing serious damage to cognitive function. Hydrogen sulfide (H₂S), the third gas signal molecule, plays important regulatory role in learning and memory functions. Inhibition of excessive autophagy and upregulation of silent information regulator 1 (Sirt-1) have been reported to prevent cognitive dysfunction. Therefore, this present work was to address whether H₂S attenuates the cognitive impairment induced by SD in Wistar rats and whether the underlying mechanisms involve in inhibition of excessive autophagy and upregulation of Sirt-1. After treatment with SD for 72 h, the cognitive function of Wistar rats was evaluated by Y-maze, new object recognition, object location, and Morris water maze tests. The results shown that SD-caused cognitive impairment was reversed by treatment with NaHS (a donor of H₂S). NaHS also prevented SD-induced hippocampal excessive autophagy, as evidenced by the decrease in autophagosomes, the down-regulation of Beclin1, and the up-regulation of p62 in the hippocampus of SD-exposed Wistar rats. Furthermore, Sirtinol, an inhibitor of Sirt-1, reversed the inhibitory roles of NaHS in SD-induced cognitive impairment and excessive hippocampal autophagy in Wistar rats. Taken together, our results suggested that H₂S improves the cognitive function of SD-exposed rats by inhibiting excessive hippocampal autophagy in a hippocampal Sirt-1-dependent way.

     

Serum protein index in human malaria

The serum protein levels were determined in 158 malarial patients infected with Plasmodium falciparum. Contrary to an earlier reported protein deficiency during malarial infection, the results obtained from this study showed no significant change (p > 0.05) in serum protein levels when compared with the controls. The significance of the results related to excessive protein catabolism in fever is discussed.     

Screening in brief intervention trials targeting excessive drinkers in general practice: systematic review and meta-analysis

Objective To determine the effectiveness of programmes of screening in general practice for excessive alcohol use and providing brief interventions.Design Systematic review and meta-analysis of randomised controlled trials that used screening as a precursor to brief intervention.Setting General practice.Main outcome measures Number needed to treat, proportion of patients positive on screening, proportion given brief interventions, and effect of screening.Results The eight studies included for meta-analysis all used health questionnaires for screening, and the brief interventions included feedback, information, and advice. The studies contained several sources of bias that might lead to overestimates of the effects of intervention. External validity was compromised because typically three out of four people identified by screening as excessive users of alcohol did not qualify for the intervention after a secondary assessment. Overall, in 1000 screened patients, 90 screened positive and required further assessment, after which 25 qualified for brief intervention; after one year 2.6 (95% confidence interval 1.7 to 3.4) reported they drank less than the maximum recommended level.Conclusions Although even brief advice can reduce excessive drinking, screening in general practice does not seem to be an effective precursor to brief interventions targeting excessive alcohol use. This meta-analysis raises questions about the feasibility of screening in general practice for excessive use of alcohol.     

A critical role of superoxide anion in selenite-induced mitophagic cell death

Mitochondria, which are a major source of intracellular reactive oxygen species (ROS), are extremely vulnerable to oxidative stress. We recently reported that selenite treatment of various glioma cells induced a non-apoptotic cell death accompanied by excessive mitophagy (selective autophagy of damaged mitochondria). Examination of various ROS revealed that the superoxide anion played a key role in selenite-induced mitochondrial damage, mitophagy and cell death. Treatment with superoxide generators (diquat and paraquat) was sufficient to trigger mitophagy in glioma cells. Small interfering RNA-mediated knockdown of ATG6 or ATG7 attenuated selenite-induced mitophagy and cell death, demonstrating that the mitophagic pathway contributes to selenite-induced cell death. The effect of selenite in glioma cells may thus provide an example of superoxide-mediated mitophagic cell death, i.e., cell death caused by excessive mitophagy.     

Excessive dietary calcium in the disruption of structural and functional status of adult male reproductive system in rat with possible mechanism

Calcium is essential for functioning of different systems including male reproduction. However, it has also been reported as chemo-castrative agent. The study has been undertaken to elucidate the effect of excessive dietary calcium on male reproductive system in animals with possible action. Adult male healthy rats fed CaCl(2) at different doses (0.5, 1.0 and 1.5 g%) in diet for 13 and 26 days to investigate reproductive parameters as well as the markers of oxidative stress. Significant alteration was found (P < 0.05) in testicular and accessory sex organs weight, epididymal sperm count, testicular steroidogenic enzyme (Δ(5) 3β-HSD and 17β-HSD) activities, serum testosterone, LH, FSH, LPO, activities of antioxidant enzymes, testicular histoarchitecture along with adrenal Δ(5) 3β-HSD activity with corticosterone level in dose- and time-dependent manner. Overall observations suggest that excessive dietary calcium enhances the generation of free-radicals resulting in structural and functional disruption of male reproduction.     

CONSEQUENCES OF SHIFTWORKING ON SLEEP DURATION,SLEEPINESS, AND SLEEP ATTACKS

Rotating shift and permanent night work arrangements are known to compromise sleep. This study examined the effects of work schedule on sleep duration, excessive sleepiness, sleep attacks, driving, and domestic/professional accidents. A representative sample of the general population of the state of New York—3,345 individuals ≥18 yrs of age—was interviewed by telephone regarding their sleep and psychiatric and organic disorders. Multivariate models were applied to derive odds ratios (OR) after adjustment for age, sex, physical illness, mental disorders, obstructive sleep apnea, and sleep duration. On average (±SE), workers slept 6.7?±?1.5?h, but 40% slept <6.5?h/main sleep episode. Short-sleep duration (<6?h) was strongly associated with fixed night (OR: 1.7) and day-evening-night shiftwork arrangement (OR: 1.9). Some 20% of the workers manifested excessive sleepiness in situations requiring high attention, and it was associated with the fixed night (OR: 3.3) and day-evening-night work arrangements (OR: 1.5). Overall, 5% of the workers reported sleep attacks; however, they occurred three-times more frequently in the fixed night (15.3%) than other work arrangements (OR: 3.2). Driving accidents during the previous 12 months were reported by 3.6% of the workers and were associated with fixed night (OR: 3.9) and day-evening-night (OR: 2.1) work schedules. The findings of this study indicate that working outside the regular daytime hours was strongly associated with shorter sleep duration, sleepiness, and driving accident risk. Night work is the most disrupting, as it is associated with insufficient sleep during the designated rest span and excessive sleepiness and sleep attacks during the span of activity, with an associated consequence being increased driving accident risk. (Author correspondence: mohayon@stanford.edu)     

Sleep length,working hours and socio-demographic variables are associated with time attending evening classes among working college students

It is the aim of the present study to assess factors associated with time spent in class among working college students. Eighty-two working students from 21 to 26 years old participated in this study. They were enrolled in an evening course of the University of São Paulo, Brazil. Participants answered a questionnaire on living and working conditions. During seven consecutive days, they wore an actigraph, filled out daily activity diaries (including time spent in classes) and the Karolinska Sleepiness Scale every three hours from waking until bedtime. Linear regression analyses were performed in order to assess the variables associated with time spent in classes. The results showed that gender, sleep length, excessive sleepiness, alcoholic beverage consumption (during workdays) and working hours were associated factors with time spent in class. Thus, those who spent less time in class were males, slept longer hours, reported excessive sleepiness on Saturdays, worked longer hours, and reported alcohol consumption. The combined effects of long work hours (>40 h/week) and reduced sleep length may affect lifestyles and academic performance. Future studies should aim to look at adverse health effects induced by reduced sleep duration, even among working students who spent more time attending evening classes.

     

Intake of beer, wine and spirits and risk of heavy drinking and alcoholic cirrhosis

Studies have suggested that wine drinkers are at lower risk of death than beer or spirit drinkers. The aim of this study is to examine whether the risk of becoming a heavy drinker or developing alcoholic cirrhosis differs among individuals who prefer different types of alcoholic beverages. In a longitudinal setting we found that both the risk of becoming a heavy or excessive drinker (above 14 and 21 drinks per week for women and above 21 and 35 drinks per week for men) and the risk of developing alcoholic cirrhosis depended on the individuals preference of wine, beer or spirits. We conclude that moderate wine drinkers appear to be at lower risk of becoming heavy and excessive drinkers and that this may add to the explanation of the reported beverage-specific differences in morbidity and mortality.     

Flubendazole induces mitochondrial dysfunction and DRP1-mediated mitophagy by targeting EVA1A in breast cancer

Breast cancer is still one of the most common malignancies worldwide and remains a major clinical challenge. We previously reported that the anthelmintic drug flubendazole induced autophagy and apoptosis via upregulation of eva-1 homolog A (EVA1A) in triple-negative breast cancer (TNBC) and was repurposed as a novel anti-tumor agent. However, the detailed underlying mechanisms remain unclear and need further investigation. Here, we found that flubendazole impairs the permeability of the mitochondrial outer membrane and mitochondrial function in breast cancer. Meanwhile, flubendazole increased dynamin-related protein (DRP1) expression, leading to the accumulation of PTEN induced putative kinase 1 (PINK1) and subsequent mitochondrial translocation of Parkin, thereby promoting excessive mitophagy. The resultant excessive mitophagy contributed to mitochondrial damage and dysfunction induced by flubendazole, thus inhibiting breast cancer cells proliferation and migration. Moreover, we demonstrated that excessive DRP1-mediated mitophagy played a critical role in response to the anti-tumor effects of EVA1A in breast cancer. Taken together, our results provide new insights into the molecular mechanisms in relation to the anti-tumor activities of flubendazole, and may be conducive to its rational use in potential clinical applications.Subject terms: Breast cancer, Pharmacology

     

Mitochondrial superoxide anion (O(2)(-)) inducible "mev-1" animal models for aging research

Most intracellular reactive oxygen species (ROS), especially superoxide anion (O(2)(-)) that is converted from oxygen, are overproduced by excessive electron leakage from the mitochondrial respiratory chain. Intracellular oxidative stress that damages cellular components can contribute to lifestyle-related diseases such as diabetes and arteriosclerosis, and age-related diseases such as cancer and neuronal degenerative diseases. We have previously demonstrated that the excessive mitochondrial O(2)(-) production caused by SDHC mutations (G71E in C. elegans, I71E in Drosophila and V69E in mouse) results in premature death in C. elegans and Drosophila, cancer in mouse embryonic fibroblast cells and infertility in transgenic mice. SDHC is a subunit of mitochondrial complex II. In humans, it has been reported that mutations in SDHB, SDHC or SDHD often result in inherited head and neck paragangliomas (PGLs). Recently, we established Tet-mev-1 conditional transgenic mice using our uniquely developed Tet-On/Off system, which equilibrates transgene expression to endogenous levels. These mice experienced mitochondrial respiratory chain dysfunction that resulted in O(2)(-) overproduction. The mitochondrial oxidative stress caused excessive apoptosis leading to low birth weight and growth retardation in the neonatal developmental phase in Tet-mev-1 mice. Here, we briefly describe the relationships between mitochondrial O(2)(-) and aging phenomena in mev-1 animal models. [BMB reports 2011; 44(5): 298-305].     

Limbic-midbrain lesions and ACTH-induced excessive grooming.

The induction of excessive grooming by intraventricular administration of ACTH_1–24 was studied in rats with lesions in midbrain-limbic structures. Such areas have been reported to be implicated in mediating ACTH-induced effects on avoidance behavior, sexual excitement or stretching and yawning. Electrolytic lesions in the septal complex, the anterior hypothalamic/preoptic area, the mammillary bodies, the amygdala, the posterior thalamus and dorsal or ventral hippocampus did not interfere with ACTH-induced excessive grooming. Lesioning of the hippocampal complex by aspiration led to an inhibition of excessive grooming depending on the degree of hippocampal damage. Amygdala and hippocampal lesions enhanced the display of stretching and yawning activity after treatment with the peptide. The data indicate differences in the neural substrates mediating the effect of ACTH on extinction of conditioned avoidance behavior, excessive grooming, sexual excitement and stretching and yawning.     

Physiological role of neutral lipid accumulation in eukaryotic microalgae under stresses

In the studies of lipid metabolism of unicellular photoautotrophic eukaryotes (microalgae), the main attention is commonly paid to polar membrane lipids and their fatty acid (FA) composition, whereas neutral lipids, represented predominantly by triacylglycerols (TAG), are insufficiently studied. As was reported recently, the role of these compounds in microalgae is not limited to their storage function. It was found that TAG are frequently involved in adaptation to environmental conditions. This review summarizes experimental data obtained so far allowing to distinguish at least three aspects of TAG adaptive function in microalgae. First, these compounds are the source of long-chain FA, the building blocks for membranes necessary for rearrangements of the photosynthetic apparatus. Second, TAG biosynthesis consumes excessive photoassimilates preventing photooxidative injuries under stresses which reduce cell capacity of photosynthesis product utilization. Third, TAG deposited as cytoplasmic oil bodies form a depot for secondary carotenoids in carotenogenic microalgae producing an optical screen protecting the cell against photodamage by excessive PAR.     

Inhibition of Fibrous Adhesion Formation in the Temporomandibular Joint of Tenascin-C Knockout Mice

Tenascin-C (TNC) is a large hexameric extracellular matrix glycoprotein that is expressed in developing organs and tumors. It has been reported that TNC is expressed in inflamed synovial membranes and deformed discs of temporomandibular joint (TMJ) disorder. However, the role of TNC in TMJ is not fully known. In this study, the role of TNC in fibrous adhesion formation of TMJ was examined using TNC knockout (TNCKO) mice. Hypermobility was produced by excessive mouth opening method on the TMJ of both wild-type (WT) and TNCKO mice. TMJ wound healing was compared histologically, and the expression of TNC, fibronectin (FN), and α-smooth muscle actin (α-SMA) in the wounded TMJ was examined by immunohistochemical and immunoblot analyses. Based on histologic analysis, fibrous adhesions were observed in the TMJ of both TNCKO and wild-type (WT) mice after excessive mouth opening. However, fibrous adhesion formation in TNCKO mice occurred later than in WT mice. TNC was expressed in the wounded TMJ disc and mandibular fossa. Although FN and α-SMA expression in the TMJ of TNCKO and WT mice was up-regulated after excessive mouth opening, FN and α-SMA protein levels were higher in WT mice at the same time points. In the wounded TMJ, TNC appears to enhance the expression of FN and α-SMA, and a lack of TNC may reduce fibrous adhesion formation in the TMJ. TNC plays an important role in TMJ wound healing, especially for wounds generated by mechanical stress.Key words: Temporomandibular joint, excessive mouth opening, fibrous adhesion, tenascin-C, fibronectin, α-smooth muscle actin     

Will hotspots conserve extra primate and carnivore evolutionary history?

Setting aside biodiversity hotspots would be especially compelling if they contained not just enormous numbers of species but also excessive evolutionary history. A recent study seemed to provide evidence for this incentive for hotspot conservation. Sechrest et al . (2002 ) reported that hotspots contain more endemic phylogenetic diversity (PD) than expected based on the numbers of primate and carnivore species they contain. We extend their analysis and revise some of their claims. For primates and threatened carnivores, we show that the original analysis was driven by a single hotspot (Madagascar) that contains an ancient endemic clade. The remaining hotspots harbour less rather than significantly more endemic PD than expected. Thus, while one hotspot contains an enormous excess of evolutionary history, the remaining hotspots do not. Our analysis reveals that the overriding influence of a single hotspot can create the misleading impression that hotspots generally contain excessive evolutionary history. Justification for the hotspot initiative should be based on robust evidence. We join others in endorsing an increased role for detailed phylogenetic analysis in conservation planning.     

Meningitis in excessive alcohol consumers acquired in the community

Etiology, risk factors, treatment and outcome of 21 cases of bacterial meningitis diagnosed in excessive alcohol consumers within 5 years of national community acquired meningitis survey in Slovakia is reported.     

Heterogeneity of the triple A syndrome and assessment of a case

Allgrove syndrome (triple A syndrome) is a rare autosomal recessive disorder characterized by achalasia, alacrima, adrenal insufficiency, and--occasionally--autonomic instability. Disease causing mutations have been found in the AAAS gene on 12q13, but no strong phenotype-genotype correlation could be found. We present a 28 year-old woman with classical systemic features of triple A syndrome with prominent neurological dysfunctions/deficits, including distal muscular atrophy, progressive muscle weakness and wasting of both legs, sensibility dysfunction, hyperreflexia and autonomic dysfunction presented with excessive sweating. DNA sequencing of the AAAS gene revealed compound heterozygosity for previously reported mutations. A similar genotype was previously reported, but with a remarkably different phenotype.