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1.
Morphologie ; 108(362): 100781, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38677263

ABSTRACT

The present article offers the facial approximation of the mummy of the ancient Egyptian adolescent named Minirdis (ca. 2300 years BP) by means of anatomical analysis of video-images and through a facial approximation protocol implemented on more historical personages. An evaluation of the mummy's endocast is also offered. A potential diagnosis of Sotos syndrome is cautiously considered but its inherent limitations are detailed. Finally, the methodology is presented as a valuable tool both for bio-historical research and for further studies on normal and pathologic morphologies of the cranio-facial district.

2.
J Cardiovasc Pharmacol ; 79(4): 431-443, 2022 04 01.
Article in English | MEDLINE | ID: mdl-34935698

ABSTRACT

ABSTRACT: The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has significant implications in patients with concomitant cardiovascular disease (CVD) because they are the population at the greatest risk of death. The treatment of such patients and complications may represent a new challenge for the fields of cardiology and pharmacology. Thus, understanding the involvement of this viral infection in CVD might help to reduce the aggressiveness of SARS-CoV-2 in causing multiorgan infection and damage. SARS-CoV-2 disturbs the host epigenome and several epigenetic processes involved in the pathophysiology of COVID-19 that can directly affect the function and structure of the cardiovascular system (CVS). Hence, it would be relevant to identify epigenetic alterations that directly impact CVS physiology after SARS-CoV-2 infection. This could contribute to the view of this virus-induced CVS injury and direct forthcoming tackles for COVID-19 treatment to reduce mortality in patients with CVD. Targeting epigenetic marks could offer strong evidence for the development of novel antiviral therapies, especially in the context of COVID-19-related CVS damage. In this review, we address some of the main signaling pathways that are currently known as being involved in COVID-19 pathophysiology and the importance of this glint on epigenetics and some of its modifiers (epidrugs) to control the unregulated epitope activity in the context of SARS-CoV-2 infection, COVID-19, and underlying CVD.


Subject(s)
COVID-19 Drug Treatment , Cardiovascular Diseases , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/genetics , Epigenesis, Genetic , Humans , SARS-CoV-2
3.
Int J Environ Sci Technol (Tehran) ; 19(10): 10375-10380, 2022.
Article in English | MEDLINE | ID: mdl-34691198

ABSTRACT

This work aimed to investigate the effect of freezing on the oleuropein content obtained from olive leaves extracts. The extracts were obtained by microwave-assisted extraction using different solvents, pH, temperatures and microwave irradiation time. Afterward, HPLC was used to identify and quantify the amount of oleuropein in the extracts. A part of the extracts was immediately analyzed, and another was frozen for a week. The experimental results highlighted that the storage condition has a significant (p < 0.05) effect on the oleuropein content. Regardless of the extraction condition, the frozen storage was responsible for a decrease in the oleuropein content, ranging from 5.38 to 70.09%. These results indicate that it is important to consider the degradation of oleuropein in frozen olive leaf extracts so that subsequent applications are suitable.

4.
J Intern Med ; 287(6): 685-697, 2020 06.
Article in English | MEDLINE | ID: mdl-32176378

ABSTRACT

Mutations in the mitochondrial genome are the cause of many debilitating neuromuscular disorders. Currently, there is no cure or treatment for these diseases, and symptom management is the only relief doctors can provide. Although supplements and vitamins are commonly used in treatment, they provide little benefit to the patient and are only palliative. This is why gene therapy is a promising research topic to potentially treat and, in theory, even cure diseases caused by mutations in the mitochondrial DNA (mtDNA). Mammalian cells contain approximately a thousand copies of mtDNA, which can lead to a phenomenon called heteroplasmy, where both wild-type and mutant mtDNA molecules co-exist within the cell. Disease only manifests once the per cent of mutant mtDNA reaches a high threshold (usually >80%), which causes mitochondrial dysfunction and reduced ATP production. This is a useful feature to take advantage of for gene therapy applications, as not every mutant copy of mtDNA needs to be eliminated, but only enough to shift the heteroplasmic ratio below the disease threshold. Several DNA-editing enzymes have been used to shift heteroplasmy in cell culture and mice. This review provides an overview of these enzymes and discusses roadblocks of applying these to gene therapy in humans.


Subject(s)
DNA Repair Enzymes/genetics , DNA, Mitochondrial/genetics , Genetic Therapy , Heteroplasmy/genetics , Animals , DNA Repair/genetics , DNA Repair Enzymes/therapeutic use , Genetic Therapy/methods , Humans , Mitochondrial Diseases
5.
J Helminthol ; 94: e46, 2019 Mar 18.
Article in English | MEDLINE | ID: mdl-30880654

ABSTRACT

Gastrointestinal nematodes significantly affect the ovine industry, and Haemonchus contortus is considered the most pathogenic parasite in tropical regions. This situation is aggravated when the main strategy to control worms fails because of the genetic resistance that parasites acquire against anthelmintics. Aiming to anticipate the events involved in anthelmintic resistance, we induced monepantel resistance in H. contortus by in vivo subdosing of sheep hosts. Four successive passages of a monepantel-susceptible H. contortus isolate in Santa Ines or Ile de France sheep hosts resulted in three monepantel-resistant (efficacy varying from 0 to 58.5%) H. contortus isolates. Sheep hosts were treated from 0.075 mg/kg to the therapeutic dose of 2.5 mg/kg of monepantel in 19-26 rounds of selection for 112-133 weeks. Success in inducing H. contortus resistance to monepantel may have been affected by worm burden and by host-parasite interactions, including a possible effect of the breed of sheep hosts. We conclude that subdosing of sheep, although time-consuming, is an efficient in vivo strategy for the induction of monepantel resistance in H. contortus. The resistant parasites can be used in further studies to elucidate the genetic and biochemical events involved in the acquisition of anthelmintic resistance.


Subject(s)
Aminoacetonitrile/analogs & derivatives , Anthelmintics/administration & dosage , Drug Resistance , Haemonchiasis/veterinary , Haemonchus/drug effects , Aminoacetonitrile/administration & dosage , Animals , Dose-Response Relationship, Drug , Female , Haemonchiasis/parasitology , Haemonchus/genetics , Male , Parasite Egg Count , Sheep , Sheep Diseases/parasitology
6.
Ophthalmology ; 125(6): 807-814, 2018 06.
Article in English | MEDLINE | ID: mdl-29310962

ABSTRACT

PURPOSE: To determine which nocturnal blood pressure (BP) parameters (low levels or extreme dipper status) are associated with an increased risk of glaucomatous damage in Hispanics. DESIGN: Observational cross-sectional study. PARTICIPANTS: A subset (n = 93) of the participants from the Maracaibo Aging Study (MAS) who met the study eligibility criteria were included. These participants, who were at least 40 years of age, had measurements for optical tomography coherence, visual field (VF) tests, 24-hour BP, office BP, and intraocular pressure <22 mmHg. METHODS: Univariate and multivariate logistic regression analyses under the generalized estimating equations (GEE) framework were used to examine the relationships between glaucomatous damage and BP parameters, with particular attention to decreases in nocturnal BP. MAIN OUTCOME MEASURES: Glaucomatous optic neuropathy (GON) based on the presence of optic nerve damage and VF defects. RESULTS: The mean age was 61.9 years, and 87.1% were women. Of 185 eyes evaluated, 19 (26.5%) had signs of GON. Individuals with GON had significantly lower 24-hour and nighttime diastolic BP levels than those without. However, results of the multivariate GEE models indicated that the glaucomatous damage was not related to the average systolic or diastolic BP levels measured over 24 hours, daytime, or nighttime. In contrast, extreme decreases in nighttime systolic and diastolic BP (>20% compared with daytime BP) were significant risk factors for glaucomatous damage (odds ratio, 19.78 and 5.55, respectively). CONCLUSIONS: In this population, the link between nocturnal BP and GON is determined by extreme dipping effects rather than low nocturnal BP levels alone. Further studies considering extreme decreases in nocturnal BP in individuals at high risk of glaucoma are warranted.


Subject(s)
Aging/physiology , Blood Pressure/physiology , Circadian Rhythm/physiology , Glaucoma, Open-Angle/physiopathology , Hypotension/physiopathology , Optic Nerve Diseases/physiopathology , Aged , Blood Pressure Monitoring, Ambulatory , Cross-Sectional Studies , Female , Glaucoma, Open-Angle/diagnosis , Gonioscopy , Humans , Intraocular Pressure/physiology , Male , Middle Aged , Nerve Fibers/pathology , Optic Nerve Diseases/diagnosis , Retinal Ganglion Cells/pathology , Tomography, Optical Coherence , Tonometry, Ocular , Venezuela , Visual Fields/physiology
7.
Public Health ; 159: 99-106, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29559184

ABSTRACT

OBJECTIVE: To present a predictive model of alcohol abuse among adolescents based on prevalence projections in various population subgroups. STUDY DESIGN: Cross-sectional study. METHODS: The sample consisted of 785 adolescents enrolled in the second year of high school in Rio de Janeiro, Brazil. Alcohol consumption was assessed using the Alcohol Use Disorder Identification Test. Socio-economic, demographic, family, individuals, and school-related variables were examined as potential predictors. The logit model was used to estimate the prevalence projections. Model fitting was examined in relation to the observed data set, and in a subset, that was generated from 200 subsamples of individuals via a bootstrap process using general fit estimators, discrimination, and calibration measures. RESULTS: About 25.5% of the adolescents were classified as positive for alcohol abuse. Being male, being 17-19 years old, not living with mothers, presenting symptoms suggestive of binge eating, having used a strategy of weight reduction in the last 3 months, and, especially, being a victim of family violence were important predictors of abusive consumption of alcohol. While the model's prevalence projection in the absence of these features was 8%, it reaches 68% in the presence of all predictors. CONCLUSIONS: Knowledge of predictive characteristics of alcohol abuse is essential for screening, early detection of positive cases, and establishing interventions to reduce consumption among adolescents.


Subject(s)
Alcohol Drinking/psychology , Alcoholism/diagnosis , Alcoholism/prevention & control , Adolescent , Alcoholism/epidemiology , Brazil/epidemiology , Cross-Sectional Studies , Early Diagnosis , Female , Humans , Logistic Models , Male , Predictive Value of Tests , Prevalence , Young Adult
8.
Ophthalmology ; 124(10): 1449-1456, 2017 10.
Article in English | MEDLINE | ID: mdl-28551166

ABSTRACT

PURPOSE: To investigate the prevalence of visual field defects in glaucomatous eyes, glaucoma suspects, and ocular hypertensives with 24-2 and 10-2 visual fields. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Patients with or suspected glaucoma tested with 24-2 and 10-2. Patients were classified into 3 groups on the basis of the presence of glaucomatous optic neuropathy (GON) and 24-2 visual field abnormalities: early glaucoma (GON and abnormal visual field, mean deviation >-6 decibels [dB]), glaucoma suspects (GON and normal visual field), and ocular hypertensives (normal disc, normal visual field, and intraocular pressure >22 mmHg). For the classification of visual field abnormalities, 24-2 and 10-2 tests performed on the same visit were analyzed. MAIN OUTCOME MEASURES: Comparison of the prevalence of abnormal 24-2 versus 10-2 visual field results based on cluster criteria in each diagnostic group. RESULTS: A total of 775 eyes (497 patients) were evaluated. A total of 364 eyes had early glaucoma, 303 eyes were glaucoma suspects, and 108 eyes were ocular hypertensives. In the glaucoma group, 16 of the 26 eyes (61.5%) classified as normal based on cluster criteria on 24-2 tests were classified as abnormal on 10-2 visual fields. In eyes with suspected glaucoma, 79 of the 200 eyes (39.5%) classified as normal on the 24-2 test were classified as abnormal on 10-2 visual fields. In ocular hypertensive eyes, 28 of the 79 eyes (35.4%) classified as normal on the 24-2 were classified as abnormal on the 10-2. Patients of African descent were more likely to have an abnormal 10-2 result (67.3 vs. 56.8%, P = 0.009). CONCLUSIONS: Central visual field damage seen on the 10-2 test is often missed with the 24-2 strategy in all groups. This finding has implications for the diagnosis of glaucoma and classification of severity.


Subject(s)
Glaucoma, Open-Angle/diagnosis , Ocular Hypertension/diagnosis , Optic Nerve Diseases/diagnosis , Visual Field Tests/standards , Visual Fields/physiology , Adult , Aged , Cross-Sectional Studies , Early Diagnosis , Ethnicity , Female , Glaucoma, Open-Angle/ethnology , Glaucoma, Open-Angle/physiopathology , Humans , Intraocular Pressure/physiology , Male , Middle Aged , Nerve Fibers/pathology , Ocular Hypertension/ethnology , Ocular Hypertension/physiopathology , Optic Nerve Diseases/ethnology , Optic Nerve Diseases/physiopathology , Prevalence , Prospective Studies , Retinal Ganglion Cells/pathology , Tonometry, Ocular , Visual Field Tests/instrumentation
9.
BMC Ophthalmol ; 16(1): 217, 2016 Dec 29.
Article in English | MEDLINE | ID: mdl-28034308

ABSTRACT

BACKGROUND: Antifibrotic agents are commonly utilized to enhance the success rates of trabeculectomy. Novel approaches to further improve success rates and reduce the risks of complications are needed. The purpose of this study was to compare intraocular pressure (IOP)-lowering efficacy and safety of trabeculectomy or combined phacoemulsification and trabeculectomy with mitomycin-C (MMC) vs. Collagen Matrix (CM). METHODS: A prospective, multicenter, randomized controlled trial was performed. Ninety-five eyes of 94 patients with uncontrolled glaucoma despite medical therapy, without previous incisional glaucoma surgery underwent trabeculectomy (85 eyes) or combined phacoemulsification and trabeculectomy (10 eyes) and were randomized to MMC or CM. One eye of each subject was analyzed. Patients were followed for 24 months. The criteria for complete success were IOP >5 and ≤21 mmHg with at least a 20% reduction below medicated baseline without additional glaucoma surgery or medications. The main outcome measures were complete success rates at 24 months with Kaplan-Meier analysis and incidence of adverse events. RESULTS: The baseline IOPs were 20.4 ± 6.0 mmHg and 21.2 ± 6.1 (mean ± standard deviation, p = 0.49) on 3.2 ± 1.1 and 3.1 ± 1.0 medications (p = 0.53) compared to 11.8 ± 5.2 and 12.8 ± 3.7 (p = 0.36) on 0.5 ± 0.8 and 0.6 ± 1.0 medications (p = 0.63) at 2 years in the MMC and CM groups, respectively. Kaplan-Meier analysis demonstrated complete success rates were similar in both groups at 24 months: 38.4 ± 7.6% with MMC and 56.2 ± 7.9% with CM (mean ± standard error, p = 0.112, log rank test); however, a significantly higher incidence of failure due to persistent hypotony was observed with MMC (p = 0.002). CONCLUSIONS: Use of the CM implant at the time of trabeculectomy or combined phacoemulsification and trabeculectomy is associated with similar complete success rates compared to adjunctive MMC; however, the risk of persistent hypotony is higher with MMC. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT01440751 . Registered 9/14/11.


Subject(s)
Antifibrinolytic Agents/therapeutic use , Collagen/therapeutic use , Glaucoma/surgery , Mitomycin/therapeutic use , Phacoemulsification , Trabeculectomy/methods , Aged , Antihypertensive Agents/therapeutic use , Combined Modality Therapy/methods , Female , Glaucoma/drug therapy , Glaucoma/physiopathology , Humans , Intraocular Pressure/physiology , Kaplan-Meier Estimate , Male , Middle Aged , Prospective Studies , Trabeculectomy/adverse effects
10.
Reprod Domest Anim ; 51(2): 204-11, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26812982

ABSTRACT

This study aimed to produce in vitro bovine embryos by the addition of two drugs, which is responsible for oocyte meiosis inhibition: roscovitine (ROS) and butyrolactone I (BL-I). Oocytes were recovered from slaughtered cows and matured in a commercial medium and maintained in a 5% CO2 atmosphere. Oocytes were maintained for 6 h in an in vitro maturation (IVM) medium containing ROS (12.5 µm), BL-I (50 µm) and association of drugs (ROS 6.25 µm and BL-I 25 µm). Oocytes were cultured for 18 h in an agent-free medium for the resumption of meiosis. After 24 h of maturation, oocytes were inseminated in the commercial in vitro fertilization (IVF) medium. Presumptive zygotes were cultured in SOFaa medium in a 5% CO2 atmosphere. On day 3, rate of cleavage was evaluated and on days 6 and 7, rate of blastocyst formation. BL-I and its association with the ROS increased the rates of cleavage and blastocyst formation (p < 0.05). The ROS alone was inefficient, impairing embryonic development, with low rates of blastocyst formation when compared to the control group and other treatments (p < 0.05). The embryos from BL-I and ROS+BL-I groups presented higher number of cells and lower rates of cellular apoptosis compared to other groups, either for the fresh or for post-thawing embryos. Embryos from ROS+BL-I group showed to be more resistant to the vitrification process, presenting a higher rate of embryonic re-expansion (p < 0.05). In conclusion, block of meiosis using BL-I or its association with ROS increased the rate of blastocyst formation, and the association of ROS+BL-I resulted in a better resistance to the embryo cryopreservation process.


Subject(s)
4-Butyrolactone/analogs & derivatives , Cattle/embryology , Embryo Culture Techniques/veterinary , Meiosis/drug effects , Protein Kinase Inhibitors/pharmacology , Purines/pharmacology , 4-Butyrolactone/administration & dosage , 4-Butyrolactone/pharmacology , Animals , Apoptosis/drug effects , Apoptosis/physiology , Cell Cycle Checkpoints/drug effects , Drug Therapy, Combination , Protein Kinase Inhibitors/administration & dosage , Purines/administration & dosage , Roscovitine
11.
J Clin Pharm Ther ; 40(3): 251-8, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25810127

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: High levels of adherence to antiretroviral therapy (ART) are needed to achieve the desired results. Because pharmaceutical care might contribute to improved adherence to treatment, the aim of this study was to assess the impact of pharmaceutical interventions on ART via a systematic review of randomized clinical trials (RCT). METHODS: Study selection, data extraction and risk-of-bias assessment were performed independently by two reviewers. RESULTS AND DISCUSSION: A total of 681 studies were located; only four of these met the inclusion criteria and were analysed. The summary measure corresponding to the outcome adherence to treatment was 1·47 (95% confidence interval [CI]: 0·81-2·65), and the measure corresponding to the outcome virologic suppression was 1·95 (95% CI: 0·61-6·25). WHAT IS NEW AND CONCLUSION: The results suggest that pharmaceutical interventions might contribute to improved adherence to ART and the achievement of virologic suppression, although the differences between the intervention and control groups were not statistically significant. Pharmaceutical interventions might be more efficacious in populations with low adherence to treatment and greater vulnerability.


Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , Medication Adherence , Anti-HIV Agents/administration & dosage , Humans , Pharmaceutical Services/organization & administration , Randomized Controlled Trials as Topic
12.
Clin Exp Ophthalmol ; 43(3): 228-33, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25214176

ABSTRACT

BACKGROUND: To evaluate the reproducibility of intraocular pressure peaks and fluctuation elicited during the water drinking test in treated glaucomatous patients with a long follow-up interval. DESIGN: Retrospective cohort study in a tertiary care practice. PARTICIPANTS: Thirty-four treated primary open-angle glaucoma patients. METHODS: All patients underwent the water drinking test performed in two consecutive visits without any change in the therapeutic regimen. The mean interval between tests was 4.85 (range: 3-6) months. Reproducibility of peak and fluctuation during the water drinking test was assessed using intraclass correlation coefficients. Bland-Altman analysis was used to assess the agreement of intraocular pressure peaks and fluctuation measured between two consecutive tests. MAIN OUTCOME MEASURES: Intraclass correlation and agreement of intraocular pressure peaks and fluctuation between visits. RESULTS: There were no significant differences in baseline intraocular pressure values (mean ± standard deviation, 11.73 ± 2.36 and 11.61 ± 2.71 mmHg; P = 0.72) and peaks (14.55 ± 3.41 and 15.02 ± 3.66 mmHg, respectively; P = 0.163) detected during the water drinking test between the first and second visits. There was also no significant difference between the average intraocular pressure fluctuation values (2.82 ± 1.99 and 3.41 ± 2.54 mmHg, respectively; P = 0.135). Intraocular pressure peaks and fluctuation presented intraclass correlation coefficients of 0.85 (P < 0.001) and 0.50 (P < 0.001), respectively. CONCLUSIONS: Our results demonstrate excellent reproducibility of intraocular pressure peaks during the water drinking test. Intraocular pressure fluctuation did not reveal good reproducibility, though. These results emphasize the applicability of this test to assess treatment efficacy in daily practice and interventional studies.


Subject(s)
Diagnostic Techniques, Ophthalmological , Drinking , Glaucoma, Open-Angle/diagnosis , Intraocular Pressure/physiology , Stress, Physiological/physiology , Adult , Aged , Aged, 80 and over , Antihypertensive Agents/therapeutic use , False Positive Reactions , Female , Follow-Up Studies , Glaucoma, Open-Angle/drug therapy , Glaucoma, Open-Angle/physiopathology , Humans , Male , Middle Aged , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies , Tonometry, Ocular , Visual Fields/physiology
13.
Ophthalmology ; 126(2): e12-e13, 2019 02.
Article in English | MEDLINE | ID: mdl-30683182
14.
Am J Ophthalmol ; 259: 7-14, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38708401

ABSTRACT

Purpose: To evaluate the diagnostic accuracy of retinal nerve fiber layer thickness (RNFLT) by spectral-domain optical coherence tomography (OCT) in primary open-angle glaucoma (POAG) in eyes of African (AD) and European descent (ED). Design: Comparative diagnostic accuracy analysis by race. Participants: 379 healthy eyes (125 AD and 254 ED) and 442 glaucomatous eyes (226 AD and 216 ED) from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. Methods: Spectralis (Heidelberg Engineering GmbH) and Cirrus (Carl Zeiss Meditec) OCT scans were taken within one year from each other. Main Outcome Measures: Diagnostic accuracy of RNFLT measurements. Results: Diagnostic accuracy for Spectralis-RNFLT was significantly lower in eyes of AD compared to those of ED (area under the receiver operating curve [AUROC]: 0.85 and 0.91, respectively, P=0.04). Results for Cirrus-RNFLT were similar but did not reach statistical significance (AUROC: 0.86 and 0.90 in AD and ED, respectively, P =0.33). Adjustments for age, central corneal thickness, axial length, disc area, visual field mean deviation, and intraocular pressure yielded similar results. Conclusions: OCT-RNFLT has lower diagnostic accuracy in eyes of AD compared to those of ED. This finding was generally robust across two OCT instruments and remained after adjustment for many potential confounders. Further studies are needed to explore the potential sources of this difference.


Subject(s)
Glaucoma, Open-Angle , Intraocular Pressure , Nerve Fibers , Optic Disk , ROC Curve , Retinal Ganglion Cells , Tomography, Optical Coherence , Visual Fields , White People , Humans , Glaucoma, Open-Angle/ethnology , Glaucoma, Open-Angle/diagnosis , Tomography, Optical Coherence/methods , Nerve Fibers/pathology , Retinal Ganglion Cells/pathology , Female , Male , Middle Aged , Intraocular Pressure/physiology , Visual Fields/physiology , White People/ethnology , Reproducibility of Results , Aged , Optic Disk/pathology , Optic Disk/diagnostic imaging , Optic Nerve Diseases/diagnosis , Optic Nerve Diseases/ethnology , Black or African American/ethnology , Area Under Curve , Sensitivity and Specificity
15.
Horm Metab Res ; 45(12): 900-4, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24013946

ABSTRACT

Irisin, a hormone secreted by myocytes induced in exercise, acts as a muscle-derived energy-expenditure signal that binds to undetermined receptors on the white adipose tissue surface, stimulating its browning and uncoupling protein 1 (UCP1) expression. The purpose of this study was to assess the effect of an intradialytic resistance exercise training program (RETP) on plasma irisin levels of hemodialysis (HD) patients and compare the baseline plasma irisin levels of HD patients to healthy subjects. This longitudinal study enrolled 26 patients undergoing HD (50% men, 44.8±14.1 years, body mass index (BMI) 23.5±3.9 kg/m²). The healthy subjects group consisted of 11 women and 7 men with mean age of 50.9±6.6 years and BMI, 24.2±2.7 kg/m². Anthropometric and biochemistry parameters (Irisin by Enzyme-Linked Immunosorbent Assay) were measured at the baseline and after 6 months of RETP (in both lower limbs). There was no difference regarding gender, age, and BMI between HD patients and healthy subjects. Plasma irisin levels in HD patients were lower than in healthy subjects (71.0±41.6 vs. 101.3±12.5 ng/ml, p<0.05). Although the muscle mass increased in consequence of exercise [evaluated by arm muscle area from 27.9 (24.1) to 33.1 (19.0) cm²], plasma irisin did not differ significantly after exercises (71.0±41.6 vs. 73.3±36.0 ng/ml). HD patients seem to have lower plasma irisin when compared to healthy subjects. Moreover, a resistance exercise training program was unable to augment plasma irisin despite increasing muscle mass.


Subject(s)
Exercise , Fibronectins/blood , Renal Dialysis , Resistance Training , Adult , Anthropometry , Female , Health , Humans , Male , Muscle Strength/physiology , Physical Fitness
16.
Nat Genet ; 28(3): 200-1, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11431681

ABSTRACT

One of three loci previously associated with autosomal dominant progressive external ophthalmoplegia (adPEO) encodes ANT1, a mitochondrial nucleotide transporter. Now, mutations in two other genes are found in people with adPEO. One of these encodes a new helicase, Twinkle, which is related to the product of bacteriophage T7 gene 4, and co-localizes with mitochondrial DNA. The identification of Twinkle adds a new star to the expanding constellation of 'helicase diseases'.


Subject(s)
DNA Primase/genetics , DNA, Mitochondrial/genetics , Ophthalmoplegia, Chronic Progressive External/genetics , DNA Helicases , Humans , Mitochondrial Proteins , Ophthalmoplegia, Chronic Progressive External/enzymology , Sequence Deletion
17.
Nat Genet ; 4(3): 284-8, 1993 Jul.
Article in English | MEDLINE | ID: mdl-7689388

ABSTRACT

We have identified an unusual mitochondrial (mt) tRNA mutation in a seven year-old girl with a pure myopathy. This G to A transition at mtDNA position 15990 changed the anticodon normally found in proline tRNAs (UGG) to the one found in serine tRNAs (UGA), and is the first pathogenic anticodon alteration described in a higher eukaryote. The mutant mtDNA was heteroplasmic (85% mutant) in muscle but was undetectable in white blood cells from the patient and her mother. Analysis of single muscle fibres indicated that mutant mtDNAs severely impaired mitochondrial protein synthesis and respiratory chain activity, but only when present at greater than 90%. The recessive behaviour of this mtDNA alteration may explain the patient's relatively mild clinical phenotype.


Subject(s)
Anticodon/genetics , Mitochondrial Myopathies/genetics , RNA/genetics , Base Sequence , Child , DNA, Mitochondrial/genetics , DNA, Mitochondrial/metabolism , Female , Humans , Mitochondrial Myopathies/metabolism , Molecular Sequence Data , Muscle Proteins/biosynthesis , Muscle Proteins/genetics , Muscles/metabolism , Pedigree , Phenotype , Point Mutation , RNA, Mitochondrial , RNA, Transfer, Pro/genetics , RNA, Transfer, Ser/genetics , Tissue Distribution
18.
Nat Genet ; 1(5): 359-67, 1992 Aug.
Article in English | MEDLINE | ID: mdl-1284549

ABSTRACT

Large-scale deletions of mitochondrial DNA (mtDNA) are associated with a subgroup of mitochondrial encephalomyopathies. We studied seven patients with Kearns-Sayre syndrome or isolated ocular myopathy who harboured a sub-population of partially-deleted mitochondrial genomes in skeletal muscle. Variable cytochrome c oxidase (COX) deficiencies and reduction of mitochondrially-encoded polypeptides were found in affected muscle fibres, but while many COX-deficient fibres had increased levels of mutant mtDNA, they almost invariably had reduced levels of normal mtDNA. Our results suggest that a specific ratio between mutant and wild-type mitochondrial genomes is the most important determinant of a focal respiratory chain deficiency, even though absolute copy numbers may vary widely.


Subject(s)
DNA, Mitochondrial/genetics , Kearns-Sayre Syndrome/genetics , Mitochondrial Myopathies/genetics , Mitochondrial Myopathies/pathology , Oculomotor Muscles/pathology , Sequence Deletion , Blotting, Southern , Cytochrome-c Oxidase Deficiency , DNA Probes , Electron Transport Complex IV/genetics , Electron Transport Complex IV/metabolism , Humans , Immunohistochemistry , In Situ Hybridization , Kearns-Sayre Syndrome/enzymology , Kearns-Sayre Syndrome/pathology , MELAS Syndrome/genetics , MERRF Syndrome/genetics , Mitochondrial Myopathies/enzymology , Oculomotor Muscles/enzymology , Polymerase Chain Reaction/methods , RNA/analysis , RNA/genetics , RNA, Mitochondrial , Succinate Dehydrogenase/genetics , Succinate Dehydrogenase/metabolism
19.
J Glaucoma ; 32(9): 721-724, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37343189

ABSTRACT

PRCIS: We evaluated 16,351 visual field (VF) tests from Ocular Hypertension Treatment Study (OHTS) database and showed that more frequent testing resulted in a shorter time to detect glaucoma progression, with the best trade-off being the 6-month intervals for high-risk and 12 months for low-risk patients. PURPOSE: To investigate the effect of different testing intervals on time to detect visual field progression in eyes with ocular hypertension. METHODS: A total of 16,351 reliable 30-2 VF tests from 1575 eyes of the OHTS-1 observation arm with a mean (95% CI) follow-up of 4.8 (4.7-4.8) years were analyzed. Computer simulations (n = 10,000 eyes) based on mean deviation values and the residuals of risk groups (according to their baseline 5 y risk of developing primary open angle glaucoma: low, medium, and high risk) were performed to estimate time to detect progression with testing intervals of 4, 6, 12, and 24 months using linear regression. The time to detect VF progression ( P < 5%) at 80% power was calculated based on the mean deviation slope of -0.42 dB/year. We assessed the time to detect a -3 dB loss as an estimate of clinically meaningful perimetric loss. RESULTS: At 80% power, based on the progression of -0.42 dB/year, the best trade-off to detect significant rates of VF change to clinically meaningful perimetric loss in high, medium, and low-risk patients was 6, 6, and 12-month intervals, respectively. CONCLUSION: Given the importance of not missing the conversion to glaucoma, the frequency of testing used in OHTS (6 mo) was optimal for the detection of progression in high-risk patients. Low-risk patients could potentially be tested every 12 months to optimize resource utilization.


Subject(s)
Glaucoma, Open-Angle , Glaucoma , Ocular Hypertension , Optic Disk , Humans , Visual Fields , Glaucoma, Open-Angle/diagnosis , Intraocular Pressure , Tonometry, Ocular , Vision Disorders/diagnosis , Visual Field Tests , Ocular Hypertension/diagnosis , Disease Progression , Follow-Up Studies
20.
JAMA Ophthalmol ; 141(10): 956-964, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37676684

ABSTRACT

Importance: Calcium channel blocker (CCB) use has been associated with an increased risk of glaucoma in exploratory studies. Objective: To examine the association of systemic CCB use with glaucoma and related traits among UK Biobank participants. Design, Setting, and Participants: This population-based cross-sectional study included UK Biobank participants with complete data (2006-2010) for analysis of glaucoma status, intraocular pressure (IOP), and optical coherence tomography (OCT)-derived inner retinal layer thicknesses. Data analysis was conducted in January 2023. Exposure: Calcium channel blocker use was assessed in a baseline touchscreen questionnaire and confirmed during an interview led by a trained nurse. Main Outcomes and Measures: The primary outcome measures included glaucoma status, corneal-compensated IOP, and 2 OCT-derived inner retinal thickness parameters (macular retinal nerve fiber layer [mRNFL] and macular ganglion cell-inner plexiform layer [mGCIPL] thicknesses). We performed logistic regression and linear regression analyses to test for associations with glaucoma status and IOP and OCT-derived inner retinal thickness parameters, respectively. Results: This study included 427 480 adults. Their median age was 58 (IQR, 50-63) years, and more than half (54.1%) were women. There were 33 175 CCB users (7.8%). Participants who had complete data for glaucoma status (n = 427 480), IOP (n = 97 100), and OCT-derived inner retinal layer thicknesses (n = 41 023) were eligible for respective analyses. After adjustment for key sociodemographic, medical, anthropometric, and lifestyle factors, use of CCBs (but not other antihypertensive agents) was associated with greater odds of glaucoma (odds ratio [OR], 1.39 [95% CI, 1.14 to 1.69]; P = .001). Calcium channel blocker use was also associated with thinner mGCIPL (-0.34 µm [95% CI, -0.54 to -0.15 µm]; P = .001) and mRNFL (-0.16 µm [95% CI, -0.30 to -0.02 µm]; P = .03) thicknesses but not IOP (-0.01 mm Hg [95% CI, -0.09 to 0.07 mm Hg]; P = .84). Conclusions and Relevance: In this study, an adverse association between CCB use and glaucoma was observed, with CCB users having, on average, 39% higher odds of glaucoma. Calcium channel blocker use was also associated with thinner mGCIPL and mRNFL thicknesses, providing a structural basis that supports the association with glaucoma. The lack of association of CCB use with IOP suggests that an IOP-independent mechanism of glaucomatous neurodegeneration may be involved. Although a causal relationship has not been established, CCB replacement or withdrawal may be considered should glaucoma progress despite optimal care.


Subject(s)
Calcium Channel Blockers , Glaucoma , Adult , Humans , Female , Middle Aged , Male , Cross-Sectional Studies , Biological Specimen Banks , UK Biobank , Retinal Ganglion Cells , Glaucoma/physiopathology
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