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PubMed2002

Abacavir substitution for nucleoside analogs in patients with HIV lipoatrophy: a randomized trial.

CONTEXT: Peripheral lipoatrophy may complicate antiretroviral therapy of human immunodeficiency virus (HIV) infection, often related to duration and type of nucleoside analog therapy, and may have a mitochondrial pathogenesis. No proven therapy exists for lipoatrophy, but abacavir is a nucleoside analog that may be less toxic to mitochondria. OBJECTIVE: To determine if substitution of stavudine or zidovudine with abacavir improves HIV lipoatrophy without affecting control of HIV replication. DESIGN: Randomized, open-label 24-week study. SETTING: Seventeen hospital HIV outpatient clinics and primary care centers in Australia and England, with randomization from June 2000 through January 2001. PARTICIPANTS: A total of 111 adults (109 men) with moderate or severe lipoatrophy who were receiving stavudine (n = 85) or zidovudine (n = 26) and had stable plasma HIV RNA levels below 400 copies/mL and no prior abacavir therapy. INTERVENTION: Patients were randomly assigned to switch from stavudine or zidovudine to abacavir, 300 mg twice per day, while continuing all other antiretroviral therapy (n = 54) or to continue all antiretroviral therapy (n = 57). MAIN OUTCOME MEASURES: The primary end point was limb fat mass, measured by dual-energy x-ray absorptiometry; key secondary end points were plasma HIV RNA levels, adverse events, physician-assessed (via subjective measures) lipodystrophy severity, total and central fat mass, and fasting metabolic (lipid, glycemic, and lactate) levels. RESULTS: There was a significant increase in limb fat in the abacavir group relative to the stavudine/zidovudine group (0.39 vs 0.08 kg; mean difference, 0.31; 95% confidence interval [CI], 0.06-0.57 kg), as well as significant relative increases in subcutaneous thigh (P =.01), arm (P<.001), and abdominal (P =.001) fat areas on computed tomography. Switching had no significant effect on secondary end points, including plasma HIV RNA (for unadjusted comparison between groups at week 24, odds ratio, 1.38; 95% CI, 0.48-3.96). Change in limb fat mass at week 24 did not correlate with change in subjectively determined perceived lipoatrophy severity (r = -0.06; P =.53 by Spearman correlation). Hypersensitivity to abacavir was seen in 5 patients (10%). CONCLUSIONS: In this sample of lipoatrophic HIV-infected adults, switching from stavudine or zidovudine to abacavir for 24 weeks led to significant, albeit modest, objectively measured increases in limb fat. Clinical lipoatrophy, as assessed subjectively, did not resolve, however, and at the rate of increase observed may take years to resolve with use of this strategy. Longer-term follow-up is needed.

Absorptiometry, Photon↗

PubMed2006

The influence of nuclear content on developmental competence of gaur x cattle hybrid in vitro fertilized and somatic cell nuclear transfer embryos.

In nondomestic and endangered species, the use of domestic animal oocytes as recipients for exotic donor nuclei causes the normal pattern of cytoplasmic inheritance to be disrupted, resulting in the production of nuclear-cytoplasmic hybrids. Evidence suggests that conflict between nuclear and cytoplasmic control elements leads to a disruption of normal cellular processes, including metabolic function and cell division. This study investigated the effects of nuclear-cytoplasmic interactions on the developmental potential of interspecies embryos produced by in vitro fertilization and somatic cell nuclear transfer: cattle x cattle, gaur x cattle, hybrid x cattle. Cattle control and hybrid embryos were examined for development to the blastocyst stage and blastocyst quality, as determined by cell number and allocation, apoptosis incidence, and expression patterns of mitochondria-related genes. These analyses demonstrated that a 100% gaur nucleus within a domestic cattle cytoplasmic environment was not properly capable of directing embryo development in the later preimplantation stages. Poor blastocyst development accompanied by developmental delay, decreased cell numbers, and aberrant apoptotic and related gene expression profiles, all signs of disrupted cellular processes associated with mitochondrial function, were observed. Developmental potential was improved when at least a portion of the nuclear genome corresponded to the inherited cytoplasm, indicating that recognition of cytoplasmic components by the nucleus is crucial for proper cellular function and embryo development. A better understanding of the influence of the cytoplasmic environment on embryonic processes is necessary before interspecies somatic cell nuclear transfer can be considered a viable alternative for endangered species conservation.

Animals↗

PubMed2003

Sublethal effects of phenol on spermatogenesis in sea urchins (Anthocidaris crassispina).

Adult sea urchins, Anthocidaris crassispina, were exposed to 0.1 and 10 mgL(-1) phenol for 4 weeks. Abnormal sperm development was clearly evident in phenol-treated sea urchins, although no mortality was found throughout the exposure period. Occurrences of multinucleate sperm cells (including spermatocytes to spermatozoa) showed a significant increase from 0.07% in the control to 10.7% and 43.3% in the 0.1- and 10-mgL(-1) treatments, respectively (P<0.01). Likewise, sperm with electron dense, dark tails increased significantly from 8% in the control to 36.6% and 43.4% in the 0.1- and 10-mgL(-1) phenol-treated sea urchins, respectively (P<0.01). In addition, disruption of cytoplasmic membranous structures such as loss of mitochondrial cristae and distortion of mitochondrial membranes and nucleus envelope were commonly found in phenol-treated spermatogonia and spermatocytes. Previous studies have clearly demonstrated motility impairment and a concomitant reduction of fertilization capability in sea urchin sperm with dark tails and/or distorted mitochondria. Our current findings therefore suggest that chronic exposure to phenol at 0.1 mgL(-1) could lower the quality of sperm and reproductive success in sea urchins, which may threaten the survival of these ecologically important species. The observed impairment of spermatogenesis by phenol might also occur in other invertebrate species.

Animals↗

PubMed1998

The biochemical, pathophysiological, and medical aspects of ubiquinone function.

Ubiquinone (Q) shares its biological implication in membrane-associated redox reactions with a variety of other redox carriers, such as dehydrogenases, non-heme-iron proteins, and cytochromes. Peculiarities arise from the lack of transition metals, which in contrast to the other electron carriers do not participate in redox-shuttle activities of Q. Another peculiarity is the lipophilicity of Q, which allows free movement between reductants and oxidants of a membrane. The chemistry of Q reduction and ubiquinol oxidation requires the stepwise acceptance and transfer of two single electrons associated with the addition or release of two single H+. These special qualities are widely used in biological membranes for linear electron transfer and transmembranous H+ translocation. In mitochondria it was long reported that under certain conditions linear e- transfer from the semireduced form (SQ.) to native oxidants of the respiratory chain may run out of control, thereby establishing a permanent source of oxygen radical release. It should be mentioned that in mitochondria e- transfer to dioxygen out of sequence requires a particular treatment with inhibitors and uncouplers of the respiratory chain. Nevertheless, it is generally assumed that Q is mainly involved in mitochondrial O2.- generation and that mitochondria represent the major source of O2.- radicals under physiological and various pathophysiological conditions. The ever-increasing application of coenzyme Q as an antioxidant for the prophylaxis and treatment of a great variety of functional disorders, including senescence, has considerably stimulated our interest in the potential prooxidative potency of this natural electron carrier. Experimental evidence will be presented that under physiological conditions Q implicated in mitochondrial e- transfer of the respiratory chain is not involved in cellular oxygen activation. It will also be shown that alterations of Q from an e- carrier to an active radical promotor is possible under various conditions. In addition, reaction products emerging from the antioxidant activity of ubiquinol were found to stimulate the formation of inorganic as well as organic oxygen radicals.

Aging↗

PubMed1980

Apparent mitochondrial creatine kinase in the serum of a patient with metastatic cancer to the liver.

Creatine kinase (CK, EC 2.7.3.2) activity in the serum of a patient with metastatic carcinoma migrated as two distinct bands cathodal to the origin and to CK-3 on agarose gel electrophoresis. The more cathodal isoenzyme (CKm-2) is of high molecular mass, is precipitated by ammonium sulfate at 30% of saturation, and is not retarded by Sephadex G-100. Treatment with urea at a concentration of 6 mol/L caused CKm-2 to elute with proteins of lower molecular mass on a G-100 column and shifted the electrophoretic migration to a position just cathodal to the origin (CKm-1). Antibody to CK-1 and CK-2 did not affect the activity of either CKm-1 or CKm-2. Similarities between these cathodal bands of CK activity and mitochondrial CK suggest the mitochondrial origin of these isoenzymes. These cathodal CK isoenzymes reacted unpredictably with different commercial reagent systems for determination of CK activity in serum or in agarose gel.

Clinical Enzyme Tests↗

PubMed1985

Biochemical rationale and the cardiac response of patients with muscle disease to therapy with coenzyme Q10.

Cardiac disease is commonly associated with virtually every form of muscular dystrophy and myopathy. A double-blind and open crossover trial on the oral administration of coenzyme Q10 (CoQ10) to 12 patients with progressive muscular dystrophies and neurogenic atrophies was conducted. These diseases included the Duchenne, Becker, and limb-girdle dystrophies, myotonic dystrophy, Charcot-Marie-Tooth disease, and Welander disease. The impaired cardiac function was noninvasively and extensively monitored by impedance cardiography. Solely by significant change or no change in stroke volume and cardiac output, all 8 patients on blind CoQ10 and all 4 on blind placebo were correctly assigned (P less than 0.003). After the limited 3-month trial, improved physical well-being was observed for 4/8 treated patients and for 0/4 placebo patients; of the latter, 3/4 improved on CoQ10; 2/8 patients resigned before crossover; 5/6 on CoQ10 in crossover maintained improved cardiac function; 1/6 crossed over from CoQ10 to placebo relapsed. The rationale of this trial was based on known mitochondrial myopathies, which involve respiratory enzymes, the known presence of CoQ10 in respiration, and prior clinical data on CoQ10 and dystrophy. These results indicate that the impaired myocardial function of such patients with muscular disease may have some association with impaired function of skeletal muscle, both of which may be improved by CoQ10 therapy. The cardiac improvement was definitely positive. The improvement in well-being was subjective, but probably real. Likely, CoQ10 does not alter genetic defects but can benefit the sequelae of mitochondrial impairment from such defects. CoQ10 is the only known substance that offers a safe and improved quality of life for such patients having muscle disease, and it is based on intrinsic bioenergetics.

Administration, Oral↗

PubMed2003

Protective effects of cyanidin-3-O-glucoside from blackberry extract against peroxynitrite-induced endothelial dysfunction and vascular failure.

Anthocyanins are a group of naturally occurring phenolic compounds as colorants in several plants, flowers and fruits. These pigments have a great importance as quality indicators, as chemotaxonomic markers and antioxidants. The content of blackberry (Rubus species) juice was investigated by HPLC/ESI/MS using narrow bore HPLC columns. Using this method we demonstrated that cyanidin-3-O-glucoside represents about 80% of the total anthocyanin contents in blackberry extract. Here we investigated antioxidant activity of the blackberry juice and cyanidin-3-O-glucoside on the endothelial dysfunction in cells and in vascular rings exposed to peroxynitrite. In human umbilical vein endothelial cells (HUVEC) in vitro, peroxynitrite caused a significant suppression of mitochondrial respiration (38 +/- 2.1% of control cells), as measured by the mitochondrial-dependent conversion of the dye MTT to formazan. Peroxynitrite caused DNA strand breakage (63 +/- 1.9% single strand vs 3 +/- 0.9% single strand in control cells), as measured by the alkaline unwinding assay, and caused an activation of PARS, as measured by the incorporation of radiolabeled NAD(+) to nuclear proteins. Blackberry juice (different dilutions that contained 80 ppm;40 ppm;14.5 ppm of cyanidin-3-O-glucoside) and cyanidin-3-O-glucoside (as chloride) (0.085 microM; 0.028 microM; 0.0085 microM) reduced the peroxynitrite-induced suppression of mitochondrial respiration, DNA damage and PARS activation in HUVECs. Vascular rings exposed to peroxynitrite exhibited reduced endothelium-dependent relaxant responses in response to acetylcholine as well as a vascular contractility dysfunction in response to norepinephrine. The development of this peroxynitrite-induced vascular dysfunction was ameliorated by the blackberry juice (different dilutions that contained 80 ppm;40 ppm;14.5 ppm of cyanidin-3-O-glucoside) and cyanidin-3-O-glucoside (as chloride) (0.085 microM;0.028 microM;0.0085 microM). In conclusion our findings clearly demonstrate that blackberry juice containing cyanidin-3-O-glucoside is a scavenger of peroxynitrite and that exert a protective effect against endothelial dysfunction and vascular failure induced by peroxynitrite.

Anthocyanins↗

PubMed2004

Decreased expression of mitochondrial genes in human unfertilized oocytes and arrested embryos.

OBJECTIVE: To evaluate the relationship between mitochondrial gene expression of oocytes/embryos and their fertilizability in unfertilized oocytes, arrested embryos, and tripronucleate zygotes, because both nuclear and cytoplasmic factors contribute to oocyte activation, fertilization, and subsequent development. DESIGN: Prospective laboratory research. SETTING: In vitro fertilization (IVF) laboratory in a university hospital. PATIENT(S): Seventy-five unfertilized oocytes, 45 arrested embryos, and 24 tripronucleate (3PN) embryos from 45 female patients undergoing IVF. INTERVENTION(S): Analysis of mitochondrial gene expression by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). MAIN OUTCOME MEASURE(S): Comparison of the expression levels of mitochondrial genes including ND2, CO I, CO II, ATPase 6, CO III, ND3, ND6, and Cyt b in three groups. RESULT(S): Significantly decreased transcription levels were expressed in unfertilized oocytes and arrested embryos. The average expression levels of the eight determined genes compared with the control (GAPDH) was 4.4 +/- 0.7, 6.4 +/- 1.1, and 13.2 +/- 1.1 in unfertilized oocytes, arrested embryos, and 3PN embryos, respectively. Significantly decreased expressions of the ATPase 6, CO III, and ND3 genes were detected from samples with 4977-bp common deletion in the mitochondrial DNA (mtDNA) compared with the non-deletion group. CONCLUSION(S): The present study is the first report to present globally decreased mitochondrial gene expression levels in human compromised oocytes and embryos. These data support the notion that the down-regulation of mitochondrial RNA by defective oxidative phosphorylation genes possibly affects oocyte quality including fertilization and further embryo development.

Base Sequence↗

PubMed2004

Toward increased utility of mtDNA in forensic identifications.

The utility of mtDNA in forensic identifications is limited by its low power of discrimination and the absence of high quality mtDNA databases. Single nucleotide polymorphisms (SNPs) in the control region outside of hypervariable regions I and II (HVI/HVII), and in the coding region of the mtDNA genome, can provide additional discrimination in mtDNA testing. We have identified particularly useful SNP sites via high throughput sequencing of the entire mtDNA genome. We report here two cases in which an 11-plex SNP assay (panel "A") targeting the most common HVI/HVII type successfully resolved two cases in which identifications could not be made on the basis of HVI/HVII sequencing. Additionally, we established a database of 286 samples for SNP panel "A" generated with robotic protocols. We have addressed the need for high quality mtDNA control region (CR) databases by developing robotic protocols for lab processing, and a carefully devised electronic data review process. A large-scale databasing effort targeting several populations underrepresented in current mtDNA databases is underway.

Complementarity Determining Regions↗

PubMed2006

Mechanisms of disease: mitochondria as new therapeutic targets in diabetic neuropathy.

Diabetic neuropathy (DN) is the most common complication of diabetes mellitus, and it imposes a considerable burden on a patient's quality of life and the health-care system. Despite the prevalence and severity of DN, there are no effective treatments. Pathogenetic evidence suggests that DN is marked by degeneration of dorsal root ganglion (DRG) neurons in peripheral nerves, and that DRG mitochondria are particularly affected. DRG mitochondria are especially vulnerable because they are the origin of reactive oxygen species production in the hyperglycemic neuron. Accumulating evidence indicates that neuronal mitochondria are subject to damage at the level of their DNA, and their outer and inner membranes, and also via deregulation of mitochondrial fission and fusion proteins that control mitochondrial shape and number. This Review will survey the mechanisms of mitochondrial degeneration in the pathogenesis of DN, highlighting potential mitochondrial sites for therapeutic intervention.

Animals↗

PubMed1994

Dithiothreitol effects on human sperm quality.

Human semen normally coagulates immediately after ejaculation and then undergoes liquefaction during the next 15 to 60 minutes. Incomplete seminal liquefaction can result in impaired sperm motility and make clinical evaluation and manipulation difficult. Dithiothreitol, a mucolytic agent that reduces the mucoprotein disulfide bonds in sputum, has been found to induce liquefaction of incompletely liquefied semen in vitro. We studied the effects of dithiothreitol on sperm motility, viability, acrosomal integrity and morphology. A semen sample was provided by 45 healthy, young men at the University of Arizona. Of the specimens 10 (22%) demonstrated incomplete liquefaction. Sperm motility and motion characteristics of untreated (control) semen and semen treated with dithiothreitol were objectively evaluated using computer assisted semen analysis. Sperm cell membrane integrity and mitochondrial integrity were measured by fluorescence microscopy using the deoxyribonucleic acid specific fluorochrome propidium iodide and the mitochondria specific fluorochrome rhodamine-123, respectively. Acrosomal integrity was determined using the fluorescent stain chlortetracycline. Sperm morphology was evaluated using bright field microscopy. For completely liquefied semen (35 cases) dithiothreitol reduced sperm motility (59.1 +/- 1.2% untreated versus 53.2 +/- 1.2% treated, p < 0.01) and motion characteristics. However, dithiothreitol had no statistically significant effect on motility on sperm in the group with incompletely liquefied semen (10 cases). Sperm cell membrane, mitochondrial and acrosomal integrity was unaffected by dithiothreitol regardless of liquefaction status. Dithiothreitol caused a significant increase in abnormally large sperm head morphology in the group with completely liquefied semen. The minimal effects of dithiothreitol on sperm motility traits and viability support its use as a possible aid in the evaluation and manipulation of incompletely liquefied semen.

Acrosome↗

PubMed1992

Identification of urinary metabolites of (+/-)-2-(p-isobutylphenyl)propionic acid (Ibuprofen) by routine organic acid screening.

Ibuprofen [(+/-)-2-(p-isobutylphenyl)propionic acid] has recently been introduced as a pediatric anti-inflammatory agent. To determine how this agent interferes with urine organic acid analysis, an important pediatric investigation, we have analyzed urine from two subjects pre- and post-Ibuprofen dosage and two subjects on chronic Ibuprofen therapy. A distinctive pattern of drug interference on the organic acid profile was detected. There were three major components, corresponding to unmetabolized Ibuprofen and to the oxidation products hydroxy Ibuprofen and carboxy Ibuprofen. Therefore, the major mechanism of Ibuprofen metabolism appears to be microsomal, although mitochondrial and peroxisomal routes cannot be excluded. Laboratories carrying out routine organic acid analysis should be aware of the nature and magnitude of the organic aciduria caused by Ibuprofen.

Adult↗

PubMed1999

Age-related alterations in liver mitochondrial bioenergetics of diabetic Goto-Kakizaki rats.

Type 2 diabetes mellitus is one of the most common chronic metabolic diseases in man. Due to long-term complications of the disease, severely decreasing the quality of life of diabetic patients, early interventions to obviate the risk of complications are of major importance. Therefore, diabetic animal models are of major importance in research for interventional treatment of type 2 diabetes. In this work we investigated the possible alterations in mitochondrial energetic metabolism of Goto-Kakizaki (GK) rats during the progression of the disease, since glucose metabolism is closely related to intracellular ATP content. For that reason, respiratory indexes (state 4, state 3, RCR and ADP/O) were evaluated either in the presence of NAD- or FAD-linked substrates (glutamate + malate and succinate, respectively) in mitochondrial preparations of GK and control rats with 8, 12, 26 and 52 weeks of age. Until the age of 1 year (52 weeks) we found no impairment of mitochondrial respiratory indexes both in the presence of glutamate + malate and succinate. In conclusion, this study indicates that GK rat is a good model for studying the initial events of diabetes, since it presents no impairment of liver mitochondrial functions during the first year of life, contrasting clearly with pharmacological induced diabetes.

Adenosine Diphosphate↗

PubMed2002

Regulation of the yeast glycine cleavage genes is responsive to the availability of multiple nutrients.

The mitochondrial glycine cleavage complex has an important role in metabolism since it provides the cell with the ability to use glycine as sole one-carbon and sole nitrogen source. In previous studies we have found that the genes encoding the unique components of this complex (GCV1, GCV2 and GCV3) are regulated by the one-carbon status of the cell. Here we have examined the transcriptional regulation of these genes with respect to nitrogen source. Two controls are required for the full range of GCV2 expression. One acts through a GATA sequence known to be involved in the control of transcription in response to the quality of the available nitrogen source and the other acts through an eight-base palindrome immediately 5' of the GATA element. This palindromic sequence previously had no known function. These data expand the repertoire of nitrogen catabolite repression to include the poor nitrogen source glycine and the genes encoding the enzyme complex responsible for its catabolism. Furthermore, deletion analyses and mutagenesis have shown that the palindromic sequence is important for full repression of GCV2 in complex glucose-containing medium and functions in a manner that is different from control mediated by the GATA element.

Amino Acid Oxidoreductases↗

PubMed2004

The role of carnitine in the male reproductive system.

Carnitine is highly concentrated in the epididymis and spermatozoa, where it may serve as an intramitochondrial vehicle for the acyl group, which in the form of acyl CoA acts as a substrate for the oxidation process producing energy for sperm respiration and motility. To date, studies in rodents and humans suggest that sperm count, motility, and maturation are related to epididymal free carnitine concentrations. Moreover, supplementation with carnitine improves sperm quality and/or quantity in testes of mice exposed to physical insults, such as heat and X-irradiation, and in men with idiopathic oligoasthenospermia. These benefits may be due to increased mitochondrial fatty acid oxidation resulting in improvement in motility of epididymal sperm. The antiapoptotic effect(s) of carnitine in the testes may also contribute, but this remains speculative and requires further investigation. Research to uncover the many characteristics and mechanisms of action of carnitine in somatic and germ cells may provide insights into the pathophysiology of germ cell apoptosis, the prevention of germ cell death, and possibly specific therapy of some forms of infertility. Further well-controlled, carefully designed, larger-scale studies are necessary and desirable before widespread clinical use as an infertility therapy can be contemplated.

Animals↗

PubMed2003

Ubiquitin-dependent proteolysis in mammalian spermatogenesis, fertilization, and sperm quality control: killing three birds with one stone.

Ubiquitin and ubiquitin-like proteins control the degradation of substrates as diverse as cyclins, viral envelope proteins, plasma membrane receptors, and mRNAs. The ubiquitinated substrates are targeted towards the lysosomal or proteasomal degradation sites. The number and position of ubiquitin molecules bound to substrates' lysine residues and the number and position of ubiquitin molecules in polyubiquitin chains determine the astonishing substrate specificity of ubiquitin-mediated proteolysis. Ubiquitin is likely to be expressed in mammalian gametes and embryos at any given developmental step, but the information on ubiquitin dependence of gametogenesis and fertilization is sketchy. Ubiquitin ligases E1, E2, E3, and UBC4 are active in the testis. Ubiquitin and proteasomal subunits can be detected in the human sperm centrosome that undergoes dramatic reduction during spermatid elongation. Spermatid histones are ubiquitinated as they are being transiently replaced by transitional proteins and permanently by protamines. Ubiquitin tagging of the sperm mitochondrial membranes may serve as a death sentence for paternal mitochondria at fertilization, thus promoting the maternal inheritance of mitochondrial DNA (mtDNA) in mammals. The defective spermatozoa become surface-ubiquitinated during sperm descent down the epididymis. Finally, new evidence suggests the involvement of ubiquitin-proteasome pathway in the zona penetration by the acrosome-reacted spermatozoon. Such differential patterns of ubiquitination in the testis and epididymis, and inside the egg, may be necessary for reproductive success in humans and animals. Deciphering and eventually manipulating the ubiquitin-dependent proteolysis in the reproductive system could allow us to redirect the mode of mtDNA inheritance after cloning and ooplasmic transplantation, provide germ line therapy in some cases of male infertility, develop new contraceptives, manage polyspermia during in vitro fertilization, and establish objective markers for infertility diagnostics, semen evaluation, and prediction of future fertility.

Animals↗

PubMed2025

Evaluating Selective Quality Control in Mammalian Oogenesis: Evidence and Opportunities.

The formation and maintenance of the finite mammalian ovarian reserve are critical for fertility and species survival. Genetic and developmental studies have uncovered various mechanisms underlying oocyte development and maturation, revealing two curious features of the ovarian germline: (a) The establishment of the follicle reserve involves an initial massive overproduction of oocyte precursors, and (b) the total number of ovulated oocytes across an animal's fertile lifetime is a very small proportion of the initial ovarian reserve. Many have proposed that this indicates the existence of selective quality control to ensure gamete fitness. Here, we review the findings underlying the hypotheses for germline quality control during prepubertal development, homeostatic fertility, and reproductive aging. We evaluate whether the existing evidence base distinguishes the active selection of specific germ cell subsets from neutral dynamics. Throughout, we discuss strategies for applying statistical frameworks to evaluate selection in oogenesis and the implications of neutrality versus selection at various points in oocyte development.

Oogenesis↗

PubMed1988

Coenzyme Q10 and key enzyme activities in papillary muscle related to left ventricle function in mitral valve disease.

Coenzyme Q10 (CoQ10) was studied in papillary muscle from 18 patients (52-67 years, 2 females) subjected to open heart surgery due to mitral valve disease. In addition the enzyme activities of lactate dehydrogenase (LD) with its five isozymes, citrate synthase (CS) and mitochondrial CK (CK-MIT) were determined. Myocardial function was assessed by means of left ventricle (LV) angiography. CoQ10 averaged 0.39 (range 0.26-0.59) micrograms x mg-1 dw. On an individual basis CoQ10 was related to CS activity although not as closely as CK-MIT (r = 0.45, p less than 0.05 versus r = 0.86, p less than 0.001). The ratio (CoQ10) x (CS activity)-1 was calculated to represent mitochondrial quality. The level of LD3 fraction increase was used to mark for the degree of metabolic stress in the heart. LD3 fraction was negatively related to the quality index (r = -0.71, p less than 0.001). Thus, those with a low CoQ10 per unit of CS activity had also a high LD3 isozyme fraction. In a subset of 12 patients with isolated mitral regurgitation due to myxomatous valve degeneration, CoQ10 and the ratio CoQ10 over CS decreased with the degree of LV function impairment (r = -0.58, p less than 0.05 and r = -0.68, p less than 0.05, respectively). The quality index takes into account not only enzyme activity but also the potential for control of free oxygen radicals.

Aged↗