966 resultados para mitochondrial dysfunction


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There has been limited previous research that has examined the views of both men with erectile dysfunction (ED) and their partners on the impact of ED on their sexuality, relationship and general functioning. The current study was designed to evaluate the above variables among men with ED and their partners. Participants for the current study were 40 heterosexual men with ED and their partners. All participants completed a questionnaire that evaluated their reaction to ED, their past and current sexual activity, their sexual and relationship satisfaction as well as their levels of self-esteem and quality of life (QOL). The results demonstrated that both men with ED and their partners reported a reduction in their levels of sexual activity since the development of ED and that they wanted to seek a solution to the problem. Men with ED demonstrated lower levels of self-esteem, QOL and sexual satisfaction than their partners but there were no differences between the partners in their level of relationship satisfaction. These findings demonstrate that ED has an impact on both the man and his partner. They also indicate the importance of including the man's partner in the assessment and treatment of ED.

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Introduction: Erectile dysfunction (ED) is a common condition estimated to affect more than 150 million men worldwide. ED should be regarded as a shared sexual problem which has significant detrimental effects both on the men who experience this condition and on their partners.
Evidence to support partner involvement in ED therapy: Evidence shows that the partner plays a key supportive role in the man's ED treatment and in successful long-term ED therapy. Including the partner in consultations may highlight discordant attitudes and communication problems between couple members which may indicate treatment acceptance or rejection, or realistic or unrealistic treatment expectations.
Options for partner involvement in ED therapy: Most patients with ED consult their physician in the absence of their partner. Therefore, involving the partner in therapy can be challenging. Two options which physicians should consider are: encouraging the patient to bring the partner into the office and, often more realistically, seeking information about, and providing information to, the partner, via the patient.
Objectives:
The objective of these recommendations is to provide practical guidance on treating couples affected by ED, and suggest techniques that may be helpful in integrating the partner into the process of ED treatment.

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Impaired glucose uptake is associated with both cardiac hypertrophy and contractile dysfunction, but whether there are common underlying  mechanisms linking these conditions is yet to be determined. Using a ‘gene dose’ Cre-Lox GLUT4-deficient murine model, we examined the effect of suppressed glucose availability on global myocardial gene expression and glycolysis substrate bypass on the function of isolated perfused hearts. Performance of hearts from 22- to 60-week-old male GLUT4 knockout (KO, > 95% reduction in GLUT4), GLUT4 knockdown (KD, 85% reduction in cardiac GLUT4) and C57Bl/6 wild-type (WT) controls was measured ex vivo in Langendorff mode perfusion. DNA microarray was used to profile mRNA expression differences between GLUT4-KO and GLUT4-KD hearts. At 22 weeks, GLUT4-KO hearts exhibited cardiac hypertrophy and impaired contractile function ex vivo, characterized by a 40% decrease in developed pressure. At 60 weeks, dysfunction was accentuated in GLUT4-KO hearts and evident in GLUT4-KD hearts. Exogenous pyruvate (5 mM) restored systolic pressure to a level equivalent to WT (GLUT4-KO, 176.8 ± 13.2 mmHg vs. WT, 146.4 ± 9.56 mmHg) in 22-week-old GLUT4-KO hearts but not in 60-week-old GLUT4-KO hearts. In GLUT4-KO, DNA microarray analysis detected downregulation of a number of genes centrally involved in mitochondrial oxidation and upregulation of other genes indicative of a shift to cytosolic β-oxidation of long chain fatty acids. A direct link between cardiomyocyte GLUT4 deficiency, hypertrophy and contractile dysfunction is demonstrated. These data provide mechanistic insight into the myocardial metabolic adaptations associated with short and long-term insulin resistance and indicate a window of opportunity for substrate intervention and functional ‘rescue’.

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• 1. The present review discusses the potential role of nitric oxide (NO) in the: (i) regulation of skeletal muscle glucose uptake during exercise; and (ii) activation of mitochondrial biogenesis after exercise.
• 2. We have shown in humans that local infusion of an NO synthase inhibitor during exercise attenuates increases in skeletal muscle glucose uptake without affecting blood flow. Recent studies from our laboratory in rodents support these findings in humans, although rodent studies from other laboratories have yielded conflicting results.
• 3. There is clear evidence that NO increases mitochondrial biogenesis in non-contracting cells and that NO influences basal skeletal muscle mitochondrial biogenesis. However, there have been few studies examining the potential role of NO in the activation of mitochondrial biogenesis following an acute bout of exercise or in response to exercise training. Early indications are that NO is not involved in regulating the increase in mitochondrial biogenesis that occurs in response to exercise.
• 4. Exercise is considered the best prevention and treatment option for diabetes, but unfortunately many people with diabetes do not or cannot exercise regularly. Alternative therapies are therefore critical to effectively manage diabetes. If skeletal muscle NO is found to play an important role in regulating glucose uptake and/or mitochondrial biogenesis, pharmaceutical agents designed to mimic these effects of exercise may improve glycaemic control.

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Uteroplacental insufficiency has been shown to impair insulin action and glucose homeostasis in adult offspring and may act in part via altered mitochondrial biogenesis and lipid balance in skeletal muscle. Bilateral uterine vessel ligation to induce uteroplacental insufficiency in offspring (Restricted) or sham surgery was performed on day 18 of gestation in rats. To match the litter size of Restricted offspring, a separate cohort of sham litters had litter size reduced to five at birth (Reduced Litter), which also restricted postnatal growth. Remaining litters from sham mothers were unaltered (Control). Offspring were studied at 6 mo of age. In males, both Restricted and Reduced Litter offspring had reduced gastrocnemius PPAR γ coactivator-1α (PGC-1 α) mRNA and protein, and mitochondrial transcription factor A (mtTFA) and cytochrome oxidase (COX) III mRNA (P < 0.05), whereas only Restricted had reduced skeletal muscle COX IV mRNA and protein and glycogen (P < 0.05), despite unaltered glucose tolerance, homeostasis model assessment (HOMA) and intramuscular triglycerides. In females, only gastrocnemius mtTFA mRNA was lower in Reduced Litter offspring (P < 0.05). Furthermore, glucose tolerance was not altered in any female offspring, although HOMA and intramuscular triglycerides increased in Restricted offspring (P < 0.05). It is concluded that restriction of growth due to uteroplacental insufficiency alters skeletal muscle mitochondrial biogenesis and metabolic characteristics, such as glycogen and lipid levels, in a sex-specific manner in the adult rat in the absence of impaired glucose tolerance. Furthermore, an adverse postnatal environment induced by reducing litter size also restricts growth and alters skeletal muscle mitochondrial biogenesis and metabolic characteristics in the adult rat.

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Nitric oxide is a potential regulator of mitochondrial biogenesis. Therefore, we investigated if mice deficient in endothelial nitric oxide synthase (eNOS-/-) or neuronal NOS (nNOS-/-) have attenuated activation of skeletal muscle mitochondrial biogenesis in response to exercise. eNOS-/-, nNOS-/- and C57Bl6 (CON) mice (16.3 ± 0.2 weeks old) either remained in their cages (basal) or ran on a treadmill (16 m min-1, 5 grade) for 60 min (n = 8 per group) and were killed 6 h after exercise. Other eNOS-/-, nNOS-/- and CON mice exercise trained for 9 days (60 min per day) and were killed 24 h after the last bout of exercise training. eNOS-/- mice had significantly higher nNOS protein and nNOS-/- mice had significantly higher eNOS protein in the EDL, but not the soleus. The basal mitochondrial biogenesis markers NRF1, NRF2α and mtTFA mRNA were significantly (P< 0.05) higher in the soleus and EDL of nNOS-/- mice whilst basal citrate synthase activity was higher in the soleus and basal PGC-1α mRNA higher in the EDL. Also, eNOS-/- mice had significantly higher basal citrate synthase activity in the soleus but not the EDL. Acute exercise increased (P< 0.05) PGC-1α mRNA in soleus and EDL and NRF2α mRNA in the EDL to a similar extent in all genotypes. In addition, short-term exercise training significantly increased cytochrome c protein in all genotypes (P< 0.05) in the EDL. In conclusion, eNOS and nNOS are differentially involved in the basal regulation of mitochondrial biogenesis in skeletal muscle but are not critical for exercise-induced increases in mitochondrial biogenesis in skeletal muscle.

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The purpose of this study was to determine whether nitric oxide synthase (NOS) inhibition decreased basal and exercise-induced skeletal muscle mitochondrial biogenesis. Male Sprague-Dawley rats were assigned to one of four treatment groups: NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME, ingested for 2 days in drinking water, 1 mg/ml) followed by acute exercise, no L-NAME ingestion and acute exercise, rest plus L-NAME, and rest without L-NAME. The exercised rats ran on a treadmill for 53 ± 2 min and were then killed 4 h later. NOS inhibition significantly (P < 0.05; main effect) decreased basal peroxisome proliferator-activated receptor-{gamma} coactivator 1beta (PGC-1beta) mRNA levels and tended (P = 0.08) to decrease mtTFA mRNA levels in the soleus, but not the extensor digitorum longus (EDL) muscle. This coincided with significantly reduced basal levels of cytochrome c oxidase (COX) I and COX IV mRNA, COX IV protein and COX enzyme activity following NOS inhibition in the soleus, but not the EDL muscle. NOS inhibition had no effect on citrate synthase or beta-hydroxyacyl CoA dehydrogenase activity, or cytochrome c protein abundance in the soleus or EDL. NOS inhibition did not reduce the exercise-induced increase in peroxisome proliferator-activated receptor-{gamma} coactivator 1{alpha} (PGC-1{alpha}) mRNA in the soleus or EDL. In conclusion, inhibition of NOS appears to decrease some aspects of the mitochondrial respiratory chain in the soleus under basal conditions, but does not attenuate exercise-induced mitochondrial biogenesis in the soleus or in the EDL.

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The current study evaluated the dropout rate from an internet-based treatment program for erectile dysfunction (ED), and determined reasons for attrition from this program. Only 12 of 40 treatment group men and 19 of 20 control group men completed the post-test measures. Reasons for the men being excluded or dropping out of the study are discussed. These reasons included medical conditions that contributed to their ED, the man's partner not being interested in participating in the program, a lack of motivation from the man, or the time commitment being too demanding.

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Sequence variation of the mitochondrial DNA 16S rRNA region of the Asian moon scallop, Amusium pleuronectes, was surveyed in seven populations along the coast of Thailand. A total of 16 unique haplotypes were detected among 174 individuals with a total 27 variable sites out of 534 bp sequenced. The mitochondrial haplotypes grouped into two distinct arrays (estimated to differ by about 2.62% to 2.99% nucleotide divergence) that characterized samples collected from the Gulf of Thailand versus the Andaman Sea. Low levels of intrapopulation variation were observed, while in contrast, significant divergence was observed between populations from the Gulf of Thailand and Andaman Sea. Results of AMOVA reveal a high F ST value (0.765) and showed that the majority of the total genetic variance (76.03%) occurred among groups (i.e., Andaman Sea and the Gulf of Thailand) and little among populations within the group (0.52%) and within populations (23.45%). The genetic differentiation between the populations recorded in the present study is similar to that observed in a variety of marine species in the Indo-Pacific. The implications of the findings for management of A. pleuronectes genetic resources in Thailand are discussed.

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Current knowledge of the evolutionary relationships among scallop species (Mollusca: Bivalvia: Pectinidae) in the Indo-Pacific region is rather scanty. To enhance the understanding of the relationships within this group, phylogenies of nine species of scallops with the majority from coastal regions of Thailand, were reconstructed by maximum parsimony, maximum likelihood, and Bayesian methods using sequences of the 16S rRNA of the mitochondrial genome, and a fragment containing the ITS1, 5.8S and ITS2 genes of the nuclear DNA. The trees that resulted from the three methods of analysis were topologically identical, however, gained different levels of support at some nodes. Nine species were clustered into two major clades, corresponding to two subfamilies (Pectininae and Chlamydinae) of the three currently recognized subfamilies within Pectinidae. Overall, the relationships reported herein are mostly in accordance with the previous molecular studies that used sequences of the mtDNA cytochrome oxidase subunit I, and the classification system based on microsculpture of shell features and morphological characteristics of juveniles. Levels of divergences were different among genes (i.e., the 5.8S gene showed the lowest levels of nucleotide divergence at all levels, whereas the 16S rRNA showed the highest level of variation within species, and ITS2 gene revealed the highest level of divergence at higher levels).

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Sexual dysfunction research has primarily focused on understanding and treating problems of erectile dysfunction (ED) in men. Research has paid little attention to the impact of ED on women. The current study reports on an investigation of women's perception of their partners' ED, what they had tried to do about the problem and the impact of ED on them and their relationship. In-depth interviews were conducted with 51 women who were currently in a heterosexual relationship with a man with ED. The findings provide detailed information on women's experience of their partners' ED. They also demonstrate the need for educational resources on sexual difficulties for both the lay public and their medical practitioners. In the clinical situation, the study demonstrated the value of involving the female partner in the treatment process in improving a couple's sexual satisfaction.

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Introduction: Several preference studies comparing a short-acting with a longer-acting phosphodiesterase type 5 inhibitor have been conducted in men. Most men in those studies preferred tadalafil rather than sildenafil, and recent post hoc analysis of one study described several factors associated with men’s treatment preference. No prospective studies have investigated the woman partners’ preferences.

Aim: To investigate the treatment preference of women who were partners of men using oral medications for erectile dysfunction (ED) in a single-center open-label crossover study.

Methods: One hundred heterosexual couples in stable relationships, with male partners having ED based on the erectile function subscale of the International Index of Erectile Function, were randomly assigned to receive sildenafil or  tadalafil for a 12-week phase, followed by another 12-week period using the alternate drug. Male and female participants completed sexual event diaries during both study phases, and the female participants were interviewed at  baseline, midpoint, and end of study.

Main Outcome Measures
: Primary outcome data were the women’s final  interviews during which they were asked which drug they preferred and their reasons for that preference.

Results: A total of 79.2% of the women preferred their partners’ use of tadalafil, while 15.6% preferred sildenafil. Preference was not affected by age or treatment order randomization. Women preferring tadalafil reported feeling more relaxed, experiencing less pressure, and enjoying a more natural or spontaneous sexual experience as reasons for their choice. Mean number of tablets used, events recorded, events per week, and days between events were not significantly different during each study phase.

Conclusion: Women’s preferences were similar to men when using these two drugs. While the women’s reasons for preferring tadalafil emphasized relaxed, satisfying, longer-lasting sexual experiences, those preferring sildenafil focused on satisfaction and drug effectiveness for their partner.

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Introduction. Many recent studies have investigated the prevalence of female sexual difficulty/dysfunction.
Aim. Investigate female sexual difficulty/dysfunction using data from prevalence studies.
Methods. We reviewed published prevalence studies excluding those that had not included each category of sexual difficulty (desire, arousal, orgasm, and pain), were based on convenience sampling, or had a response rate <50% or a sample size <100.
Main Outcome Measures. For each study we used the prevalence of any sexual difficulty as the denominator and calculated the proportion of women reporting each type of difficulty. For each category of sexual difficulty we used the prevalence of that difficulty lasting 1 month or more as the denominator and calculated the proportion of difficulties lasting several months or more and 6 months or more.
Results. Only 11 of 1,248 studies identified met our inclusion criteria. These studies used different measures of sexual dysfunction, so generating a simple summary prevalence was not possible. However, we observed consistent patterns in the published data. Among women with any sexual difficulty, on average, 64% (range 16–75%) experienced desire difficulty, 35% (range 16– 48%) experienced orgasm difficulty, 31% (range 12–64%) experienced arousal difficulty, and 26% (range 7–58%) experienced sexual pain. Of the sexual difficulties that occurred for 1 month or more in the previous year, 62–89% persisted for at least several months and 25–28% persisted for 6 months or more. Two studies investigated distress. Only a proportion of women with sexual difficulty were distressed by it (21–67%).
Conclusions. Desire difficulty is the most common sexual difficulty experienced by women. While the majority of difficulties last for less than 6 months, up to a third persist for 6 months or more. Sexual difficulties do not always cause distress. Consequently, prevalence estimates will vary depending on the time frame specified by researchers and whether distress is included in these estimates.