Resistance Training with Instability in Multiple System Atrophy: A Case Report

This case report assessed quality of life, activities of daily living, motor symptoms, functional ability, neuromuscular parameters and mRNA expression of selected genes related to muscle protein synthesis and degradation in a patient with Multiple System Atrophy (MSA). The patient underwent resistance training with instability devices (i.e., bosu, dyna disk, balance disk, Swiss ball) for six months twice a week. After the six months training, the patient’s left and right quadriceps muscle cross-sectional area and leg press one-repetition maximum increased 6.4%, 6.8%, and 40%, respectively; the patient’s timed up and go, sit to stand, dynamic balance, and activities of daily living improved 33.3%, 28.6%, 42.3%, and 40.1%, respectively; the patient’s severity of motor symptoms and risk of falls decreased 32% and 128.1%, respectively. Most of the subscales of quality of life demonstrated improvements as well, varying from 13.0% to 100.0%. mRNA expression of mechanogrowth factor and mammalian target of rapamycin increased 12.7-fold and 1.5-fold, respectively. This case report describes likely the first nonpharmacological therapeutic tool that might be able to decrease the severity of motor symptoms and risk of falls, and to improve functional ability, neuromuscular parameters, and quality of the life in a patient with MSA.

Key points

• Six months of resistance training with instability alleviate the MSA-related effects and improve the quality of life in a patient with MSA.
• High complexity exercise intervention (i.e., resistance training with instability) may be very beneficial to individuals with impaired motor control and function as MSA patients.
• Caution should be exercised when interpreting our findings as they cannot be generalized to the entire MSA population and they do not allow establishing causal conclusions on the effects of this mode of exercise on MSA.

Key words: Exercise training, risk of falls, motor symptoms, cross-sectional area     

Effect of opicapone and entacapone upon levodopa pharmacokinetics during three daily levodopa administrations

Background and objectives

Opicapone is a novel third generation catechol-O-methyltransferase (COMT) inhibitor. The purpose of this study was to compare the levodopa pharmacokinetic profile throughout a day driven by the COMT inhibition either following repeated doses of opicapone or concomitant administration with entacapone.

Methods

A randomized, double-blind, gender-balanced, parallel-group study was performed in 4 groups of 20 healthy subjects each. Four subjects in each group received placebo during the entire study. Sixteen subjects in one group received placebo once daily for 11 days and on day 12, 200 mg entacapone concomitantly with each levodopa/carbidopa dose (three times separated by a 5-h interval). Sixteen subjects in each of the remaining three groups received respectively 25, 50, and 75 mg opicapone once daily for 11 days and on day 12, placebo concomitantly with each levodopa/carbidopa dose.

Results

Levodopa minimum plasma concentration (C_min) for each levodopa/carbidopa dose and for the mean of all levodopa/carbidopa doses increased substantially with all active treatments (entacapone and opicapone) when compared to the control group (placebo), with values ranging from 1.7-fold (200 mg entacapone) to 3.3-fold (75 mg opicapone). No statistical difference was found for levodopa peak of systemic exposure (as assessed by maximum observed plasma concentration (C_max)) between all active treatments and placebo. A significant increase in the levodopa extent of systemic exposure (as assessed by concentration-time curve (AUC)) occurred with all opicapone treatments in relation to placebo. No statistical difference was found for levodopa AUC when entacapone was compared to placebo. When compared to entacapone, both 50 and 75 mg opicapone presented a significant increase for the levodopa AUC. All active treatments significantly inhibited both peak (as assessed by E_max) and extent (as assessed by effect-time curve (AUEC)) of the COMT activity in relation to placebo. When compared to entacapone, all opicapone treatments significantly decreased the extent (AUEC) of the COMT activity due to a long-lasting and sustained effect. The tolerability profile was favorable for all active treatments.

Conclusion

Opicapone, a novel third generation COMT inhibitor, when compared to entacapone, provides a superior response upon the bioavailability of levodopa associated to more pronounced, long-lasting, and sustained COMT inhibition. The tolerability profile was favorable. On the basis of the results presented in this study and along with the earlier pharmacology studies, it is anticipated that opicapone adjunct therapy at the dosages of 25 and 50 mg will provide an enhancement in levodopa availability that will translate into clinical benefit for Parkinson’s disease patients.     

Single nucleotide polymorphisms (SNPs) at -238 and -308 positions in the TNFalpha promoter: clinical and bacteriological evaluation in leprosy

Tumor necrosis factor alpha (TNFalpha) plays a key role in orchestrating the complex events involved in inflammation and immune response. The presence of single nucleotide polymorphisms (SNPs) within the promoter region of the TNFa gene has been associated with a number of diseases. The aim of this study was to investigate the distribution of polymorphisms at positions -238 (G/A) and -308 (G/A) at the TNFalpha promoter, and its association to the outcome of different clinical forms of leprosy. Furthermore, the bacteriological index (BI) was evaluated among genotyped multibacillary (MB) patients in order to investigate the possible influence of each polymorphism on the bacterial load. This study included a total of 631 leprosy patients being 401 MB and 230 paucibacillary (PB), that was further separated according to its ethnicity (Afro- and Euro-Brazilians). The combination of SNPs in haplotypes generated three different arrangements: TNFG-G, TNFG-A and TNFA-G. In spite of the marked differences observed in the frequency of the haplotypes along the ethnic groups, no statistical differences were observed in haplotype frequencies between MB and PB patients. The BI analyses showed a lower bacteriological index among the -308 carriers, while the BI of the -238 carriers was higher. Although no significance has been achieved in this analysis regarding the influence of the polymorphisms to the development of the clinical outcome, it seems that in a different stage (among the MB patients) the polymorphisms could contribute to the degree of severity observed.     

Chronic adaptations of lung function in breath-hold diving fishermen

Objectives

The aim of this study was to verify and analyze the existence of chronic adaptations of lung function in free-diving fishermen whose occupation is artisanal fishing.

Material and Methods

This was a cross-sectional study involving 11 breath-hold diving fishermen and 10 non-breath-hold diving fishermen (control) from the village of Bitupitá in the municipality of Barroquinha (Ceará — Brazil). Anthropometric measurements, chest and abdominal circumferences as well as spirometric and respiratory muscle strength tests were conducted according to the specifications of the American Thoracic Society/European Respiratory Society (ATS/ERS). In order to compare the measured values versus the predicted values, Student t test was used in the case of parametric test and Wilcoxon test in the case of nonparametric test. To compare the inter-group means Student t test was used for parametric test and Mann-Whitney test for the nonparametric one. The level of significance was set at α = 5%.

Results

The forced vital capacity (FVC) (4.9±0.6 l vs. 4.3±0.4 l) and forced expiratory volume in 1 s (FEV₁) (4.0±0.5 l vs. 3.6±0.3 l) were, respectively, higher in the group of divers compared to the control group (p ≤ 0.05). Furthermore, in the group of free divers, the measured FVC, FEV₁ and FEV₁/FVC ratios were significantly greater than the predicted ones. No differences were found between the measured respiratory pressures.

Conclusions

These results indicate that breath-hold diving seems to produce chronic adaptations of the respiratory system, resulting in elevated lung volumes with no airway obstruction.     

Bone tissue reaction,setting time,solubility, and pH of root repair materials

Clinical Oral Investigations - This study aims to compare the bone tissue reaction, setting time, solubility, and pH of NeoMTA Plus, Biodentine (BD), and MTA Angelus (MTA-A). Initial and final...     

Type I Tympanoplasty: surgical success and prognostic factors

ObjectivesTo evaluate success rate of type I tympanoplasty in adults and to investigate the importance of selected prognostic factors on graft uptake.Material and methodsRetrospective medical chart review of 155 patients who underwent Type I Tympanoplasty, in our department, from January 2013 to December 2017. Graft uptake rate was evaluated and the effects of prognostic factors on surgical outcome such as sex, smoking and otological surgery history, status of the contralateral ear, size and location of the perforation, middle ear mucosa status, surgical approach and graft material. Preoperative and postoperative audiometric data were collected, and the functional success was determined.ResultsThe overall surgical anatomical success rate was 75%. Analysis of the selected variables, identified as independent prognostic factors of anatomical unsuccess (95% CI): smoking (OR = 3.29, p < .01), middle ear tympanosclerosis (OR = 2.96; p = .04). Perforations above 50% of the tympanic membrane area had a borderline effect on graft uptake (p = .05). There was a significative improvement in the average air conduction thresholds of 7.44 dB and an ABG closure rate at 10 dB and 20 dB was achieved in 47% and 84.5%, respectively. Patients who received temporalis fascia graft had similar hearing gain compared to patients who underwent cartilage tympanoplasty (7.7 vs. 7.3 dB, p = .79).ConclusionType I tympanoplasty is an effective and safe procedure with a high anatomical success rate in the treatment of mucosal COM. Poorer outcomes were found in patients with smoking habits, in those with tympanosclerosis of middle ear mucosa and in larger perforations. These prognostic factors should be considered in surgical planning and patients should be advised to quit smoking. Tympanoplasty with cartilage graft had a hearing outcome comparable to temporalis fascia graft and should be considered in high-risk patients.     

Dynamics of anti‐human leukocyte antigen antibodies after renal transplantation and their impact on graft outcome

The purpose of this study was to sequentially monitor anti‐HLA antibodies and correlate the results with antibody‐mediated rejection (AMR), graft survival (GS), and graft function (GF). We collected sera from 111 kidney transplant recipients on transplant days 0, 7, 14, 30, 60, 90, 180, and 360 and analyzed PRA levels by ELISA. DSAs were analyzed by single‐antigen beads in rejecting kidneys. At pre‐transplant, 79.3% of the patients were non‐sensitized (PRA = 0%) and 20.7% were sensitized (PRA > 1%). After transplant, patients were grouped by PRA profile: no anti‐HLA antibodies pre‐ or post‐transplant (group HLApre?/post?; n = 80); de novo anti‐HLA antibodies post‐transplant (group HLApre?/post+; n = 8); sensitized pre‐transplant/increased PRA post‐transplant (group HLApre+/post↑; n = 9); and sensitized pre‐transplant/decreased PRA post‐transplant (group HLApre+/post↓; n = 14). De novo anti‐HLA antibodies were detected at 7–180 d. In sensitized patients, PRA levels changed within the first 30 d post‐transplant. Incidence of AMR was higher in HLApre?/post+ and HLApre+/post↑ than in HLApre?/post?, and HLApre+/post↓ (p < 0.001) groups. One‐yr death‐censored GS was 36% in group HLApre+/post↑, compared with 98%, 88% and 100% in groups HLApre?/post?, HLApre?/post+, and HLApre+/post↓, respectively (p < 0.001). Excluding first‐year graft losses, GF and GS were similar among the groups. In conclusion, post‐transplant antibody monitoring can identify recipients at higher risk of AMR.     

The benefits of a high-intensity aquatic exercise program (HydrOS) for bone metabolism and bone mass of postmenopausal women

This study aimed to evaluate the 24-week effects of a high-intensity aquatic exercise program on bone remodeling markers and bone mass of postmenopausal women. In this randomized, controlled trial we studied 108 women (58.8 ± 6.4 years), randomized into Aquatic Exercise Group (AEG), n = 64, performing 24 weeks of aquatic exercises, and Control Group (CG), n = 44, sedentary. They had their fasting morning blood sample collected for the measures of intact parathyroid hormone (iPTH), procollagen type 1 amino-terminal propeptide (P1NP) and carboxy-terminal cross-linking telopeptide of type I collagen (CTx). Bone mass was measured by dual-energy X-ray absorptiometry before and after the intervention. Participants of both groups received a daily supplementation of 500 mg of elementary calcium and 1,000 IU of vitamin D (cholecalciferol). Results showed an augment in bone formation marker (P1NP) only in the AEG (15.8 %; p = 0.001), and although both groups experienced significant enhancements in bone resorption marker (CTx), this increase was less considerable in the AEG (15 % in the AEG and 29 % in the CG). IPTH was increased by 19 % in the CG (p = 0.003) at the end. The femoral trochanter BMD presented a 1.2 % reduction in the CG (p = 0.009), whereas in the AEG no change was observed (p = 0.069). The proposed aquatic exercise program was efficient in attenuating bone resorption raise and enhancing bone formation, which prevented the participants in the AEG from reducing the femoral trochanter BMD, as happened in the CG.