Effects of therapeutic ultrasound on the mechanical properties of skeletal muscles after contusion

CONTEXTUALIZAÇÃO: O ultra-som terapêutico (UST) é um recurso comumente aplicado na aceleração do reparo tecidual de lesões musculares. A absorção das ondas ultra-sônicas é determinada pela freqüência e pela intensidade, sendo que, em uma mesma intensidade, a profundidade atingida por 1MHz é maior quando comparada a 3MHz. OBJETIVO: Analisar o comportamento das propriedades mecânicas de músculos submetidos à lesão aguda por impacto e tratados com UST, utilizando as freqüências de 1 e 3MHz. MATERIAIS E MÉTODOS: Foram utilizadas 40 ratas Wistar (200,1±17,8g), divididas em quatro grupos: (1) controle; (2) lesão muscular sem tratamento; (3) lesão muscular tratada com UST de freqüência 1MHz (0,5W/cm²) e (4) lesão muscular tratada com UST de freqüência 3MHz (0,5W/cm²). A lesão foi provocada no músculo gastrocnêmio por mecanismo de impacto. O tratamento foi de cinco minutos diários durante seis dias consecutivos. Os músculos foram submetidos a ensaios mecânicos de tração em uma máquina universal de ensaios. RESULTADOS: As médias e desvios-padrão das propriedades mecânicas dos grupos lesionados e tratados com UST foram significativamente maiores quando comparadas ao grupo lesionado sem tratamento (p<0,05). Em destaque, a propriedade de rigidez que, com a aplicação do UST, teve acréscimo de aproximadamente 38%. CONCLUSÕES: A intervenção, por meio do UST, promoveu aumento das propriedades mecânicas nos músculos lesionados aproximando-as do grupo controle. Entretanto, não foi observada diferença significativa entre as propriedades mecânicas dos grupos tratados com ultra-som de freqüências 1MHz e 3MHz.BACKGROUND: Therapeutic ultrasound is a resource commonly applied to speed up tissue repair in muscle injuries. The absorption of the ultrasound waves is determined by their frequency and intensity. For a given intensity, the depth reached by 1MHz is greater than the depth reached by 3MHz. OBJECTIVE: To analyze the mechanical properties of muscles subjected to acute impact injury treated with therapeutic ultrasound at the frequencies of 1 and 3MHz. METHODS: Forty female Wistar rats (200.1±17.8g) were used, divided into four groups: (1) control; (2) muscle injury without treatment; (3) muscle injury treated with therapeutic ultrasound at the frequency of 1MHz (0.5W/cm²); and (4) muscle injury treated with therapeutic ultrasound at the frequency of 3MHz (0.5W/cm²). The injury was produced in the gastrocnemius muscle by means of an impact mechanism. The treatment consisted of a single five-minute session per day, for six consecutive days. The muscles were subjected to mechanical traction tests in a universal test machine. RESULTS: Means and standard deviations for the mechanical properties of the injured groups that received therapeutic ultrasound were significantly greater than those of the injured group without treatment (p<0.05). The property of stiffness should be highlighted: the application of therapeutic ultrasound increased muscle stiffness by approximately 38%. CONCLUSIONS: Therapeutic ultrasound increased the mechanical properties of the injured muscles, and brought them to a level close to the control group. However, no significant difference in mechanical properties was observed between the groups treated with ultrasound at the frequencies of 1MHz and 3MHz

Primary immunodeficiency

Primary immunodeficiency disorder (PID) refers to a heterogeneous group of over 130 disorders that result from defects in immune system development and/or function. PIDs are broadly classified as disorders of adaptive immunity (i.e., T-cell, B-cell or combined immunodeficiencies) or of innate immunity (e.g., phagocyte and complement disorders). Although the clinical manifestations of PIDs are highly variable, most disorders involve at least an increased susceptibility to infection. Early diagnosis and treatment are imperative for preventing significant disease-associated morbidity and, therefore, consultation with a clinical immunologist is essential. PIDs should be suspected in patients with: recurrent sinus or ear infections or pneumonias within a 1 year period; failure to thrive; poor response to prolonged use of antibiotics; persistent thrush or skin abscesses; or a family history of PID. Patients with multiple autoimmune diseases should also be evaluated. Diagnostic testing often involves lymphocyte proliferation assays, flow cytometry, measurement of serum immunoglobulin (Ig) levels, assessment of serum specific antibody titers in response to vaccine antigens, neutrophil function assays, stimulation assays for cytokine responses, and complement studies. The treatment of PIDs is complex and generally requires both supportive and definitive strategies. Ig replacement therapy is the mainstay of therapy for B-cell disorders, and is also an important supportive treatment for many patients with combined immunodeficiency disorders. The heterogeneous group of disorders involving the T-cell arm of the adaptive system, such as severe combined immunodeficiency (SCID), require immune reconstitution as soon as possible. The treatment of innate immunodeficiency disorders varies depending on the type of defect, but may involve antifungal and antibiotic prophylaxis, cytokine replacement, vaccinations and bone marrow transplantation. This article provides a detailed overview of the major categories of PIDs and strategies for the appropriate diagnosis and management of these rare disorders

Randomized phase III trial of bleomycin, vindesine, mitomycin-C, and cisplatin (BEMP) versus cisplatin (P) in disseminated squamous-cell carcinoma of the uterine cervix: an EORTC Gynecological Cancer Cooperative Group study

PURPOSE: Three previous mitomycin-cisplatin-based chemotherapy trials conducted within the EORTC Gynecological Cancer Cooperative Group (GCCG) in patients with disseminated squamous-cell carcinoma of the uterine cervix (SCCUC) suggested that with such regimens a higher overall response rate and a higher complete response rate could be obtained compared to what might have been expected from cisplatin alone. In that respect the combination of bleomycin, vindesine (Eldesine), mitomycin C and cisplatin (BEMP) was the most promising. In the present study BEMP has been compared with the best single agent, cisplatin (P) in the expectation that improved response rates might translate into a better survival. PATIENTS AND METHODS: Eligible patients were those with SCCUC and disseminated measurable disease outside previously irradiated areas, aged < or = 75 years, with a WHO performance status < or = 2 and adequate bone marrow, renal, hepatic and pulmonary function, who gave consent according to regulations followed in individual institutions. Patients were randomized to BEMP: E 3 mg/m2 day 1, P 50 mg/m2 day 1, B 15 mg (24-hour infusion) day 2-4 and M 8 mg/m2 (at alternate cycles), or P 50 mg/m2. The first four cycles were given every 3 weeks (induction phase). Subsequent cycles were given every four weeks (maintenance phase), during which B was deleted from BEMP (MEP). Patients failing on P could be treated with BEM. Of the 287 patients entered, 235 were eligible and 201 evaluable for response. RESULTS: BEMP induced a significantly higher response rate than P (42% vs. 25%, P = 0.006). There was no difference in complete response rate (11% vs. 7%). BEMP was significantly more toxic than P (+/- BEM), both with respect to hematologic and nonhematologic toxicities. After a median follow-up of 6.1 years, survival curves were not significantly different. Median progression-free survival and overall survival were 5.3 and 10.1 months with BEMP and 4.5 and 9.3 months with P (+/- BEM), respectively. In a multivariate analysis of prognostic factors for survival, a lower age (P = 0.003), a lower performance status (P = 0.0001) and a short (<1 year) interval since diagnosis (P = 0.0152) were all associated with an increased risk of dying. For progression-free survival, lower age, prior radiotherapy, locoregional involvement and no prior surgery were associated with a high risk. Treatment with BEMP or P had no significant impact on survival, but for progression-free survival there was a trend in favor of BEMP (P = 0.0893). Adjusting for prognostic factors did not change the effect of treatment. CONCLUSIONS: Combination chemotherapy with BEMP produces more toxicity and more responses compared with cisplatin alone in patients with disseminated SCCUC, but this does not translate into a better survival. Therefore, in the palliative setting single-agent cisplatin should remain the standard therapy for these patients

Analgesic action of laser therapy (LLLT) in an animal model

OBJECTIVES: To evaluate the analgesic effect of laser therapy on healthy tissue of mice.STUDY DESIGN: Forty-five animals were divided in three groups of 15: A--infrared laser irradiation (830 nm, Kondortech, São Carlos, SP, Brazil); B--red laser irradiation (660 nm, Kondortech, São Carlos, SP, Brazil); C-- ham irradiation with laser unit off. After laser application, the mice remained immobilized for the injection of 30 microl of 2% formalin in the plantar pad of the irradiated hind paw. The time that the mouse kept the hind paw lifted was measured at 5 min intervals for 30 minutes.RESULTS: Results showed statistically significant differences comparing the control group with the infrared laser group at 5, 20, 25 and 30 accumulated minutes, and with the red laser group at all time points. The analysis of partial times, at each 5 minutes, showed statistically significant differences between the control and the laser groups up to 20 minutes.CONCLUSIONS: Laser therapy had an analgesic effect and red laser had the best results

Inferring adaptive codon preference to understand sources of selection shaping codon usage bias.

Alternative synonymous codons are often used at unequal frequencies. Classically, studies of such codon usage bias (CUB) attempted to separate the impact of neutral from selective forces by assuming that deviations from a predicted neutral equilibrium capture selection. However, GC-biased gene conversion (gBGC) can also cause deviation from a neutral null. Alternatively, selection has been inferred from CUB in highly expressed genes, but the accuracy of this approach has not been extensively tested, and gBGC can interfere with such extrapolations (e.g., if expression and gene conversion rates covary). It is therefore critical to examine deviations from a mutational null in a species with no gBGC. To achieve this goal, we implement such an analysis in the highly AT rich genome of Dictyostelium discoideum, where we find no evidence of gBGC. We infer neutral CUB under mutational equilibrium to quantify “adaptive codon preference,” a nontautologous genome wide quantitative measure of the relative selection strength driving CUB. We observe signatures of purifying selection consistent with selection favoring adaptive codon preference. Preferred codons are not GC rich, underscoring the independence from gBGC. Expression-associated “preference” largely matches adaptive codon preference but does not wholly capture the influence of selection shaping patterns across all genes, suggesting selective constraints associated specifically with high expression. We observe patterns consistent with effects on mRNA translation and stability shaping adaptive codon preference. Thus, our approach to quantifying adaptive codon preference provides a framework for inferring the sources of selection that shape CUB across different contexts within the genome

Ciprofibrate increases cholesteryl ester transfer protein gene expression and the indirect reverse cholesterol transport to the liver

<p>Abstract</p> <p>Background</p> <p>CETP is a plasma protein that modulates atherosclerosis risk through its HDL-cholesterol reducing action. The aim of this work was to examine the effect of the PPARα agonist, ciprofibrate, on the CETP gene expression, in the presence and absence of apolipoprotein (apo) CIII induced hypertriglyceridemia, and its impact on the HDL metabolism.</p> <p>Results</p> <p>Mice expressing apo CIII and/or CETP and non-transgenic littermates (CIII, CIII/CETP, CETP, non-Tg) were treated with ciprofibrate during 3 weeks. Drug treatment reduced plasma triglycerides (30-43%) and non-esterified fatty acids (19-47%) levels. Cholesterol (chol) distribution in plasma lipoprotein responses to ciprofibrate treatment was dependent on the genotypes. Treated CIII expressing mice presented elevation in VLDL-chol and reduction in HDL-chol. Treated CETP expressing mice responded with reduction in LDL-chol whereas in non-Tg mice the LDL-chol increased. In addition, ciprofibrate increased plasma post heparin lipoprotein lipase activity (1.3-2.1 fold) in all groups but hepatic lipase activity decreased in treated CETP and non-Tg mice. Plasma CETP activity and liver CETP mRNA levels were significantly increased in treated CIII/CETP and CETP mice (30-100%). Kinetic studies with ³H-cholesteryl ether (CEt) labelled HDL showed a 50% reduction in the ³H-CEt found in the LDL fraction in ciprofibrate treated compared to non-treated CETP mice. This means that ³H-CEt transferred from HDL to LDL was more efficiently removed from the plasma in the fibrate treated mice. Accordingly, the amount of ³H-CEt recovered in the liver 6 hours after HDL injection was increased by 35%.</p> <p>Conclusion</p> <p>Together these data showed that the PPARα agonist ciprofibrate stimulates CETP gene expression and changes the cholesterol flow through the reverse cholesterol transport, increasing plasma cholesterol removal through LDL.</p

Reverse Myocardial Remodeling in Hypertrophic Cardiomyopathy: Little Explored Benefit of Exercise

International Journal of Exercise Science 14(2): 1018-1026, 2021. Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease that causes myocardial remodeling. Physical exercise (PE) is a therapeutic resource used in Supervised Cardiac Rehabilitation (SCR) to improve Quality of Life (QL), reducing cardiovascular morbidity and mortality. Therefore, the aim of this study is to report how SCR using a personalized exercise prescription, promoted Reverse Myocardial Remodeling (RMR), improved functionality and QL of a patient with HCM. This is a case report of a 43-year-old sedentary female patient with a Body Mass Index (BMI) of 24.7 kg/m2. The patient was diagnosed with Septal Type Asymmetric HCM. Heart Failure (HF) grade III / IV, according to the New York Heart Association (NYHA), was initially treated with 40mg of Propranolol Hydrochloride twice a day, and presented with excessive fatigue, and angina. The echocardiogram showed a final diastolic volume (FDV) of 130 ml, a final systolic volume (FSV) of 44 ml, a left ventricular mass (LVM) of 236 g, interventricular septum thickness of 14 mm, left ventricular posterior wall (LVPW) thickness of 9 mm, left atrium diameter 46 mm, left ventricular end diastolic diameter of 52mm, septum/left ventricular wall ratio of 1.55 mm, and ejection fraction (EF) of 66% (Teicholz). It was obtained as a result of decreased FDV 130 vs. 102ml, decreased FSV 44 vs. 32 ml, decreased LVM 236 vs. 201 g, increased EF 66 vs. 69%, 26% improvement in QL, and 50% reduction in the dosage of Propranolol Hydrochloride. These results suggest that a personalized SCR program is an adjuvant treatment capable of promoting RMR and improving QL and functionality in a patient with HCM

Molecular cytogenetic characterisation of a mosaic add(12)(p13.3) with an inv dup(3)(q26.31 --> qter) detected in an autistic boy

BACKGROUND: Inverted duplications (inv dup) of a terminal chromosome region are a particular subset of rearrangements that often results in partial tetrasomy or partial trisomy when accompanied by a deleted chromosome. Associated mosaicism could be the consequence of a post-zygotic event or could result from the correction of a trisomic conception. Tetrasomies of distal segments of the chromosome 3q are rare genetic events and their phenotypic manifestations are diverse. To our knowledge, there are only 12 cases reported with partial 3q tetrasomy. Generally, individuals with this genomic imbalance present mild to severe developmental delay, facial dysmorphisms and skin pigmentary disorders. RESULTS: We present the results of the molecular cytogenetic characterization of an unbalanced mosaic karyotype consisting of mos 46,XY,add(12)(p13.3) [56]/46,XY [44] in a previously described 11 years old autistic boy, re-evaluated at adult age. The employment of fluorescence in situ hybridization (FISH) and multicolor banding (MCB) techniques identified the extra material on 12p to be derived from chromosome 3, defining the additional material on 12p as an inv dup(3)(qter --> q26.3::q26.3 --> qter). Subsequently, array-based comparative genomic hybridization (aCGH) confirmed the breakpoint at 3q26.31, defining the extra material with a length of 24.92 Mb to be between 174.37 and 199.29 Mb. CONCLUSION: This is the thirteenth reported case of inversion-duplication 3q, being the first one described as an inv dup translocated onto a non-homologous chromosome. The mosaic terminal inv dup(3q) observed could be the result of two proposed alternative mechanisms. The most striking feature of this case is the autistic behavior of the proband, a characteristic not shared by any other patient with tetrasomy for 3q26.31 --> 3qter. The present work further illustrates the advantages of the use of an integrative cytogenetic strategy, composed both by conventional and molecular techniques, on providing powerful information for an accurate diagnosis. This report also highlights a chromosome region potentially involved in autistic disorders

Gastrointestinal helminths in calves and cows in an organic milk production system

The main aim of this study was to determine the distribution of populations of gastrointestinal helminths in lactating crossbred cows and calves during the grazing season in an organic milk production system. In addition, the potential importance of the peripartum in relation to the parasite load was examined. Between January 2007 and December 2008, parasitological fecal examinations were performed on cattle belonging to the Integrated Animal Production Program of Embrapa Agrobiology. The cows' parasite load remained low during the study period, and there were no statistical differences (p > 0.05) in comparisons between the seasons. The average egg count showed a positive correlation (0.80) with the peripartum, such that egg elimination per gram (p < 0.05) was higher during the week of labor than during the pre and postpartum periods. Calves showed low parasite loads, with significantly higher egg elimination (p < 0.05) during the winter. The study indicated that infection with gastrointestinal helminths was not a limiting factor for milk production in the organic system. Specifically, it was concluded that the nematode load can be maintained at moderate levels throughout the production system, even in the absence of anthelmintic treatment