Circulating skeletal muscle related microRNAs profile in Piedmontese cattle during different age.

Piedmontese cattle is known for double-muscle phenotype. MicroRNAs (miRNAs) play important role as regulators in skeletal muscle physiological processes, and we hypothesize that plasma miRNAs expression profiles could be affected by skeletal muscle growth status related to age. Plasma samples of cattle were collected during four different ages from first week of life until the time of commercial end of the fattening period before slaughter. Small-RNA sequencing data analysis revealed the presence of 40% of muscle-related miRNAs among the top 25 highly expressed miRNAs and, 19 miRNAs showed differential expression too. Using qRT-PCR, we validated in a larger bovine population, miRNAs involved in skeletal muscle physiology pathways. Comparing new-born with the other age groups, miR-10b, miR-126-5p, miR-143 and miR-146b were significantly up-regulated, whereas miR-21-5p, miR-221, miR-223 and miR-30b-5p were significantly down-regulated. High expression levels of miR-23a in all the groups were found. Myostatin, a negative regulator of skeletal muscle hypertrophy, was predicted as the target gene for miR-23a and miR-126-5p and we demonstrated their direct binding. Correlation analysis revealed association between miRNAs expression profiles and animals' weights along the age. Circulating miRNAs could be promising for future studies on their biomarker potentialities to beef cattle selection.

Association between adenotonsillar hypertrophy and leptin, ghrelin and IGF-1 levels in children.

OBJECTIVE: Developmental and growth retardation is a condition that is often encountered among children with adenotonsillar hypertrophy (ATH). Leptin, ghrelin and IGF-1 are important factors in growth and development for children. The aim of the study was to investigate serum leptin, ghrelin and IGF-1 levels in children with ATH compare with healthy controls. MATERIAL METHOD: 82 children between ages 6-12 were included in this study, divided into two groups. The first group being the study-group consisted of 42 children with obstructive adenotonsillar hypertrophy and the second group being the control-group consisted of 40 healthy children. At 08:30 a.m., peripheral blood samples were extracted from children from both groups to examine the serum levels, and kept in -40 °C until the Elisa test. RESULTS: Leptin serum level of the control-group was found to be statistically significantly higher than the serum leptin level of the ATH group (p = 0,049; p < 0.05). Body mass indexes of the children with ATH were found to be statistically significantly lower than the body mass index (BMI) of the control group (p = 0,001; p < 0.05). In contrast, there was no statistically significant difference between ghrelin and IGF-1 levels between the ATH and control group (p = 0.193, p > 0.05 and p = 0.478, p > 0.05, respectively). CONCLUSION: Upper airway infections are common in children with ATH. Increased airway infections and obstructive enlarged adenotonsillar lymphoid tissue which are caused swallowing difficulties can lead to reduced oral intake and fat tissue. It has led us to think that, ghrelin levels may be increasing secondary to these problems in children with ATH. Furthermore, BMI and leptin would be lower in children with ATH, considering adipose tissue was lesser and leptin was being synthesized and oscillated out of the fat cells of the tissue in these children.

Adipose Tissue Hypertrophy, An Aberrant Biochemical Profile and Distinct Gene Expression in Lipedema.

BACKGROUND: Lipedema is a common adipose tissue disorder affecting women, characterized by a symmetric subcutaneous adipose tissue deposition, particularly of the lower extremities. Lipedema is usually underdiagnosed, thus remaining an undertreated disease. Importantly, no histopathologic or molecular hallmarks exist to clearly diagnose the disease, which is often misinterpreted as obesity or lymphedema. MATERIALS AND METHODS: The aim of the present study is to characterize in detail morphologic and molecular alterations in the adipose tissue composition of lipedema patients compared with healthy controls. Detailed histopathologic and molecular characterization was performed using lipid and cytokine quantification as well as gene expression arrays. The analysis was conducted on anatomically matched skin and fat tissue biopsies as well as fasting serum probes obtained from 10 lipedema and 11 gender and body mass index-matched control patients. RESULTS: Histologic evaluation of the adipose tissue showed increased intercellular fibrosis and adipocyte hypertrophy. Serum analysis showed an aberrant lipid metabolism without changes in the circulating adipokines. In an adipogenesis gene array, a distinct gene expression profile associated with macrophages was observed. Histologic assessment of the immune cell infiltrate confirmed the increased presence of macrophages, without changes in the T-cell compartment. CONCLUSIONS: Lipedema presents a distinguishable disease with typical tissue architecture and aberrant lipid metabolism, different to obesity or lymphedema. The differentially expressed genes and immune cell infiltration profile in lipedema patients further support these findings.

IgG4-type Multiple Myeloma with Diffuse Enlargement of the Thyroid Requiring Differentiation from IgG4-related Disease.

We herein report a 65-year-old man with elevated serum IgG4 levels, enlarged thyroid, and renal dysfunction, mimicking IgG4-related disease (IgG4-RD). The definitive diagnosis of IgG4-RD was not established because a tissue biopsy revealed no IgG4-positive cell infiltration or fibrosis. The presence of an M peak in the ß fraction, Bence Jones protein in urine, and progressive anemia suggested multiple myeloma (MM). The κ/λ ratio was >100, tumor plasma cells were present at >20% in bone marrow, and immunostaining revealed IgG4-positive plasma cells; therefore, he was diagnosed with IgG4-type MM. Patients with elevated IgG4 levels with no significant mass lesions should undergo systemic examinations to exclude malignancy.

Characterization of Novel Nonobese Type 2 Diabetes Rat Model with Enlarged Kidneys.

A variety of animal models of diabetes mellitus (DM) are required to study the genetics and pathophysiology of DM. We established a novel rat strain showing nonobese type 2 diabetes with enlarged kidneys from the LEA.PET-pet congenic strain and named it Diabetes with Enlarged Kidney (DEK). The body growth of DEK affected rats was similar to that of normal rats before the development of DM but was attenuated with the deterioration of DM. There was a marked difference in the etiology of DEK by gender: DM phenotypes including polyuria, polydipsia, and hyperglycemia (nonfasting blood glucose over 300 mg/dl) were found in male rats aged over 10 weeks but not in female rats. The cumulative incidence of DM in DEK males at the age of 30 weeks was 44.8%. Oral glucose tolerance tests showed glucose intolerance and decreased insulin secretion in response to glucose loading in affected males, features which were exacerbated with age. Affected males exhibited disorganized architecture of pancreatic islets, decreased numbers of ß cells, and markedly decreased expression of insulin, despite no pathological findings of hemorrhage or infiltration of inflammatory cells in the pancreatic islet. Age-related islet fibrosis appeared similar in normal and affected males. Affected males also showed enlarged kidneys with dilation of renal tubules in both the cortex and medulla, but no obvious glomerular lesions typical of diabetic nephropathy (DN) at the age of 30 weeks. Plasma levels of urea nitrogen and creatinine were normal, but hypoalbuminemia was detected. These pathophysiological features in affected males indicated that their renal function was almost maintained despite severe DM. Taken together, these findings indicate that the affected males of the DEK strain are a novel nonobese type 2 diabetes rat model useful for studying the mechanisms underlying ß cell loss and identifying genetic factors protective against DN.

Spinal IgG4-Related Hypertrophic Pachymeningitis with Spinal Cord Compression: Case Report and Literature Review.

BACKGROUND: Back pain is a leading reason for patients to seek medical attention. Although musculoskeletal causes are common, patients can also present with rarer etiologies. CASE DESCRIPTION: A 50-year-old man presented with 2 months of isolated upper back pain initially suspected to be secondary to overuse muscular strain. During the next 3 months, his pain worsened, and he developed lower extremity dysesthesia and subjective weakness, despite normal neurological examination findings. Nonrevealing laboratory workup included normal muscle enzymes, C-reactive protein, urinalysis, and human leukocyte antigen B27. Magnetic resonance imaging revealed a normal brain but a hypointense C7-T5 epidural mass, prompting a neurosurgical recommendation for laminectomy with evacuation of the suspected hematoma. His symptoms fully and promptly resolved after a 5-day course of prednisone 40 mg. When his symptoms recurred within 2 months, he underwent T4-T5 laminectomy with biopsy of a mass confluent with the dura mater. Initial pathological examination revealed fibrotic tissue of unclear etiology with polyclonal lymphoid infiltrate but no malignant cells, vasculitis, or granulomas. After months of recurrent, steroid-responsive symptoms, he presented to the rheumatology clinic. Repeat spinal magnetic resonance imaging demonstrated progression of epidural thickening with suspected spinal cord compression. Previous biopsy samples were then immunostained for IgG4, revealing focally dense IgG4-positive plasma cells, up to 29 cells per high power field, consistent with spinal IgG4-related hypertrophic pachymeningitis. He began rituximab therapy with a prednisone taper and demonstrated symptomatic and neurologic improvement with successful withdrawal from corticosteroids. CONCLUSIONS: To the best of our knowledge, the present case represents the 12th reported case of spinal IgG4-related hypertrophic pachymeningitis. An early diagnosis and treatment could prevent progression to permanent neurological impairment and functional disability.

Gestational Gigantomastia Complicated by PTHrP-Mediated Hypercalcemia.

Context: Gestational gigantomastia is an uncommon condition characterized by abnormal and excessive growth of breast tissue during an otherwise uncomplicated pregnancy. Gestational gigantomastia may be accompanied by hypercalcemia, which in some cases has been associated with elevated serum levels of PTHrP. The source of the PTHrP in these cases has been suggested to be the enlarged breasts. Objective: To describe the rapid resolution of hypercalcemia and normalization of serum PTHrP after elective termination of pregnancy, indicating that the placenta was the source of the PTHrP. Design: A retrospective analysis of clinical and biochemical data over a 2-year interval and review of literature. Setting: An academic medical center. Patient: A 33-year-old G8P4 female who presented at week 8 of pregnancy with gestational gigantomastia and subsequently developed marked hypercalcemia at week 13. Serum levels of PTH were suppressed but circulating PTHrP was elevated. There was no history of hypercalcemia or significant breast growth during previous pregnancies. Intervention: Hypercalcemia was poorly responsive to IV saline, prednisone, calcitonin, and cinacalcet. She requested termination of pregnancy at week 20. Results: Serum levels of calcium, PTH, and PTHrP normalized within 48 hours of termination of pregnancy. Conclusion: The rapid resolution of hypercalcemia after termination of pregnancy, despite persistent gigantomastia, provides evidence for a pathologic role of the placenta in the excess production of PTHrP, possibly through an as yet uncharacterized placenta-breast hormonal axis.

Circulating biomarkers of hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy assessed by cardiac magnetic resonance.

BACKGROUND: Myocardial fibrosis in hypertrophic cardiomyopathy (HCM) is associated with worse clinical outcomes. The availability of circulating biomarkers of myocardial fibrosis and hypertrophy would be helpful in clinical practice. OBJECTIVE: The aim of this study was to evaluate usefulness of various biomarkers of myocardial fibrosis and hypertrophy in HCM. METHODS: Levels of biomarkers: soluble ST2 (sST2), galectin-3 (Gal-3), growth differentiation factor-15 (GDF-15), NT-proBNP and high-sensitivity cardiac troponin T (hs-cTnT) were measured in 60 patients with HCM. All patients underwent cardiac magnetic resonance imaging to calculate parameters of hypertrophy and fibrosis. RESULTS: We observed positive correlations among sST2 levels and left ventricular mass (LVM) (r = 0.32, p = 0.012), LV mass indexed for the body surface area (LVMI) (r = 0.27, p = 0.036) and maximal wall thickness (MWT) (r = 0.31, p = 0.015). No correlation was found between Gal-3 and GDF-15 levels and hypertrophy and fibrosis parameters. We observed positive correlations among hs-cTnT levels and LVM (r = 0.58, p < 0.0001), LVMI (r = 0.48, p = 0.0001), MWT (r = 0.31, p = 0.015) and late gadolinium enhancement (LGE) mass (r = 0.37, p = 0.003). There were positive correlations between NT-proBNP levels and LVM (r = 0.33, p = 0.01), LVMI (r = 0.41, p = 0.001), MWT (r = 0.42, p < 0.001) and LGE mass (r = 0.44, p < 0.001). CONCLUSIONS: Although no correlation between sST2 levels and myocardial fibrosis was found, sST2 may provide some additional information about hypertrophy extension. NT-proBNP and hs-cTnT are useful biomarkers in assessment of hypertrophy and fibrosis in HCM.

Effects of drop set resistance training on acute stress indicators and long-term muscle hypertrophy and strength.

BACKGROUND: We investigated the effects of 2 different resistance training (RT) protocols on muscle hypertrophy and strength. The first group (N.=8) performed a single drop set (DS) and the second group (N.=8) performed 3 sets of conventional RT (normal set, NS). METHODS: Eight young men in each group completed 6 weeks of RT. Muscle hypertrophy was assessed via magnetic resonance imaging (MRI) and strength via 12 repetition maximum tests before and after the 6 weeks. Acute stress markers such as muscle thickness (MT), blood lactate (BL), maximal voluntary contraction (MVC), heart rate (HR) and rating of perceived exertion (RPE) have been measured before and after one bout of RT. RESULTS: Both groups showed significant increases in triceps muscle cross-sectional area (CSA) (10.0±3.7%, effect size (ES) =0.47 for DS and 5.1±2.1%, ES=0.25 for NS). Strength increased in both groups (16.1±12.1%, ES=0.88 for DS and 25.2±17.5%, ES=1.34 for NS). Acute pre/post measurements for one bout of RT showed significant changes in MT (18.3±5.8%, P<0.001) and MVC (-13.3±7.1, P<0.05) in the DS group only and a significant difference (P<0.01) in RPE was observed between groups (7.7±1.5 for DS and 5.3±1.4 for NS). CONCLUSIONS: Superior muscle gains might be achieved with a single set of DS compared to 3 sets of conventional RT, probably due to higher stress experienced in the DS protocol.

Effect of administration of high-protein diet in rats submitted to resistance training.

PURPOSE: Although there is limited evidence regarding the pathophysiological effects of a high-protein diet (HD), it is believed that this type of diet could overload the body and cause damage to the organs directly involved with protein metabolism and excretion. The aim of this study was to verify the effects of HD on biochemical and morphological parameters of rats that completed a resistance training protocol (RT; aquatic jump) for 8 weeks. METHODS: Thirty-two adult male Wistar rats were divided into four groups (n = 8 for each group): sedentary normal protein diet (SN-14%), sedentary high-protein diet (SH-35%), trained normal protein diet (TN-14%), and trained high-protein diet (TH-35%). Biochemical, tissue, and morphological measurements were made. RESULTS: Kidney (1.91 ± 0.34) and liver weights (12.88 ± 1.42) were higher in the SH. Soleus muscle weight was higher in the SH (0.22 ± 0.03) when compared to all groups. Blood glucose (123.2 ± 1.8), triglycerides (128.5 ± 44.0), and HDL cholesterol levels (65.7 ± 20.9) were also higher in the SH compared with the other experimental groups. Exercise reduced urea levels in the trained groups TN and TH (31.0 ± 4.1 and 36.8 ± 6.6), respectively. Creatinine levels were lower in TH and SH groups (0.68 ± 0.12; 0.54 ± 0.19), respectively. HD negatively altered renal morphology in SH, but when associated with RT, the apparent damage was partially reversed. In addition, the aquatic jump protocol reversed the damage to the gastrocnemius muscle caused by the HD. CONCLUSIONS: A high-protein diet promoted negative metabolic and morphological changes, while RT was effective in reversing these deleterious effects.

Natural History of Contralateral Hypertrophy in Patients with Multicystic Dysplastic Kidneys.

PURPOSE: We evaluated predictive factors for compensatory hypertrophy and renal outcomes in a large cohort of patients with multicystic dysplastic kidneys. MATERIALS AND METHODS: We conducted a retrospective review from 1997 to 2016. Contralateral kidney and multicystic dysplastic kidney length were recorded from all ultrasounds as well as creatinine when available. We used generalized estimating equations to determine predictors of contralateral kidney length. RESULTS: A total of 443 children with multicystic dysplastic kidneys were identified based on sonographic findings and lack of function on nuclear scan. Average followup was 3.2 years (IQR 1.5 to 5.7). Median time to involution in patients diagnosed before age 2 years was 5.5 years (95% CI 3.8-7.0). In all patients the median time to contralateral hypertrophy was 2.7 years (95% CI 2.2-3.3), and 90% of patients manifested contralateral hypertrophy by 10 years. After adjusting for age, gender, multicystic dysplastic kidney side and cohort status for each year of involution after age 2 years, the contralateral kidney grows 0.35 cm longer (95% CI 0.01-0.68, p = 0.04) compared to cases without involution. Patients with contralateral hypertrophy had greater creatinine clearance at followup (83 vs 61 ml per minute, p = 0.07), although this finding was not statistically significant due to limited data. CONCLUSIONS: The majority of children with multicystic dysplastic kidneys will have contralateral hypertrophy by age 3 years. Multicystic dysplastic kidney involution predicts contralateral kidney growth rate after age 2 years. A small cohort of patients with multicystic dysplastic kidneys will not exhibit contralateral hypertrophy and may be at risk for renal insufficiency.

Increased Adipocyte Size, Macrophage Infiltration, and Adverse Local Adipokine Profile in Perirenal Fat in Cushing's Syndrome.

OBJECTIVE: To analyze changes in fat cell size, macrophage infiltration, and local adipose tissue adipokine profiles in different fat depots in patients with active Cushing's syndrome. METHODS: Subcutaneous (SC) and perirenal (PR) adipose tissue of 10 patients with Cushing's syndrome was compared to adipose tissue of 10 gender-, age-, and BMI-matched controls with regard to adipocyte size determined by digital image analysis on hematoxylin and eosin stainings, macrophage infiltration determined by digital image analysis on CD68 stainings, and adipose tissue leptin and adiponectin levels using fluorescent bead immunoassays and ELISA techniques. RESULTS: Compared to the controls, mean adipocyte size was larger in PR adipose tissue in patients. The percentage of macrophage infiltration of the PR adipose tissue and PR adipose tissue lysate leptin levels were higher and adiponectin levels were lower in SC and PR adipose tissue lysates in patients. The adiponectin levels were also lower in the SC adipose tissue supernatants of patients. Associations were found between the severity of hypercortisolism and PR adipocyte size. CONCLUSIONS: Cushing's syndrome is associated with hypertrophy of PR adipocytes and a higher percentage of macrophage infiltration in PR adipose tissue. These changes are associated with an adverse local adipokine profile.

Normal bone density and trabecular bone score, but high serum sclerostin in congenital generalized lipodystrophy.

CONTEXT: Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a rare autosomal recessive syndrome characterized by a difficulty in storing lipids in adipocytes, low body fat mass, hypoleptinemia, and hyperinsulinemia. Sclerostin is a product of SOST gene that blocks the Wnt/ß-catenin pathway, decreasing bone formation and enhancing adipogenesis. There are no data about sclerostin in people with BSCL. OBJECTIVE: We aimed to evaluate serum sclerostin, bone mineral density (BMD), and L1-L4 Trabecular Bone Score (TBS) in BSCL patients, generating new knowledge about potential mechanisms involved in the bone alterations of these patients. DESIGN, SETTING, AND PATIENTS: In this cross-sectional study, we included 11 diabetic patients with BSCL (age 24.7±8.1years; 6 females). Sclerostin, leptin, L1-L4 TBS, BMD were measured. Potential pathophysiological mechanisms have been suggested. RESULTS: Mean serum sclerostin was elevated (44.7±13.4pmol/L) and was higher in men than women (55.3±9.0 vs. 35.1±8.4pmol/L, p=0.004). Median of serum leptin was low [0.9ng/mL (0.5-1.9)]. Seven out of 11 patients had normal BMD, while four patients had high bone mass (defined as Z-score>+2.5SD). Patients on insulin had lower sclerostin (37.3±9.2 vs. 52.6±13.4pmol/L, p=0.05). The mean TBS was 1.402±0.106, and it was higher than 1.300 in nine patients. CONCLUSIONS: Patients with lipoatrophic diabetes (BSCL) have high serum concentrations of sclerostin, normal or high BMD, and reasonable trabecular bone mass measured by TBS. This is the first report of high sclerostin and good bone microarchitecture (TBS) in BSCL patients.

Relationship between the Balance of Hypertrophic/Hyperplastic Adipose Tissue Expansion and the Metabolic Profile in a High Glucocorticoids Model.

Adipose tissue (AT) expansion is the result of two processes: hyperplasia and hypertrophy; and both, directly or indirectly, depend on the adipogenic potential of adipocyte precursor cells (APCs). Glucocorticoids (GCs) have a potent stimulatory effect on terminal adipogenesis; while their effects on early stages of adipogenesis are largely unknown. In the present work, we study, in a model of high GC levels, the adipogenic potential of APCs from retroperitoneal AT (RPAT) and its relationship with RPAT mass expansion. We employed a model of hyper-adiposity (30- and 60-day-old rats) due to high endogenous GC levels induced by neonatal treatment with l-monosodium glutamate (MSG). We found that the RPAT APCs from 30-day-old MSG rats showed an increased adipogenic capacity, depending on the APCs' competency, but not in their number. Analyses of RPAT adipocyte diameter revealed an increase in cell size, regardless of the rat age, indicating the prevalence of a hypertrophic process. Moreover, functional RPAT alterations worsened in 60-day-old rats, suggesting that the hyperplastic AT expansion found in 30-day-old animals might have a protective role. We conclude that GCs chronic excess affects APCs' adipogenic capacity, modifying their competency. This change would modulate the hyperplastic/hypertrophic balance determining healthy or unhealthy RPAT expansion and, therefore, its functionality.

Effects of Light-Emitting Diode Therapy on Muscle Hypertrophy, Gene Expression, Performance, Damage, and Delayed-Onset Muscle Soreness: Case-control Study with a Pair of Identical Twins.

OBJECTIVE: The aim of this study was to verify how a pair of monozygotic twins would respond to light-emitting diode therapy (LEDT) or placebo combined with a strength-training program during 12 weeks. DESIGN: This case-control study enrolled a pair of male monozygotic twins, allocated randomly to LEDT or placebo therapies. Light-emitting diode therapy or placebo was applied from a flexible light-emitting diode array (λ = 850 nm, total energy = 75 J, t = 15 seconds) to both quadriceps femoris muscles of each twin immediately after each strength training session (3 times/wk for 12 weeks) consisting of leg press and leg extension exercises with load of 80% and 50% of the 1-repetition maximum test, respectively. Muscle biopsies, magnetic resonance imaging, maximal load, and fatigue resistance tests were conducted before and after the training program to assess gene expression, muscle hypertrophy and performance, respectively. Creatine kinase levels in blood and visual analog scale assessed muscle damage and delayed-onset muscle soreness, respectively, during the training program. RESULTS: Compared with placebo, LEDT increased the maximal load in exercise and reduced fatigue, creatine kinase, and visual analog scale. Gene expression analyses showed decreases in markers of inflammation (interleukin 1ß) and muscle atrophy (myostatin) with LEDT. Protein synthesis (mammalian target of rapamycin) and oxidative stress defense (SOD2 [mitochondrial superoxide dismutase]) were up-regulated with LEDT, together with increases in thigh muscle hypertrophy. CONCLUSIONS: Light-emitting diode therapy can be useful to reduce muscle damage, pain, and atrophy, as well as to increase muscle mass, recovery, and athletic performance in rehabilitation programs and sports medicine.

A putative low-carbohydrate ketogenic diet elicits mild nutritional ketosis but does not impair the acute or chronic hypertrophic responses to resistance exercise in rodents.

We examined whether acute and/or chronic skeletal muscle anabolism is impaired with a low-carbohydrate diet formulated to elicit ketosis (LCKD) vs. a mixed macronutrient Western diet (WD). Male Sprague-Dawley rats (9-10 wk of age, 300-325 g) were provided isoenergetic amounts of a LCKD or a WD for 6 wk. In AIM 1, basal serum and gastrocnemius assessments were performed. In AIM 2, rats were resistance exercised for one bout and were euthanized 90-270 min following exercise for gastrocnemius analyses. In AIM 3, rats voluntarily exercised daily with resistance-loaded running wheels, and hind limb muscles were analyzed for hypertrophy markers at the end of the 6-wk protocol. In AIM 1, basal levels of gastrocnemius phosphorylated (p)-rps6, p-4EBP1, and p-AMPKα were similar between diets, although serum insulin (P < 0.01), serum glucose (P < 0.001), and several essential amino acid levels (P < 0.05) were lower in LCKD-fed rats. In AIM 2, LCKD- and WD-fed rats exhibited increased postexercise muscle protein synthesis levels (P < 0.0125), but no diet effect was observed (P = 0.59). In AIM 3, chronically exercise-trained LCKD- and WD-fed rats presented similar increases in relative hind limb muscle masses compared with their sedentary counterparts (12-24%, P < 0.05), but there was no between-diet effects. Importantly, the LCKD induced "mild" nutritional ketosis, as the LCKD-fed rats in AIM 2 exhibited ∼1.5-fold greater serum ß-hydroxybutyrate levels relative to WD-fed rats (diet effect P = 0.003). This study demonstrates that the tested LCKD in rodents, while only eliciting mild nutritional ketosis, does not impair the acute or chronic skeletal muscle hypertrophic responses to resistance exercise.

Compensatory function of the remaining testis is dissociated in boys and adolescents with monorchidism.

OBJECTIVE: Compensatory hypertrophy has been classically described in patients with monorchidism. However, it remains unclear whether there is a functional compensatory activity of the different cell populations. Our aim was to assess the functional capacity of the solitary testis in monorchid males from infancy through puberty in order to determine whether the remaining gonad is capable of compensating the functional activity of Sertoli and Leydig cells of the absent gonad. DESIGN: In a retrospective, cross-sectional, analytical study performed at a tertiary paediatric public hospital, we included 89 boys with monorchidism and 358 healthy controls, aged 6 months-18 years. Testicular volume and circulating levels of reproductive hormones were compared between patients with monorchidism and normal boys. Serum anti-Müllerian hormone (AMH) and FSH were used as biomarkers of the functional mass of prepubertal Sertoli cells, whereas serum testosterone and LH were used as biomarkers of Leydig cells. RESULTS: In the vast majority of the cases, the testicular volume of monorchid boys was smaller than the sum of the volume of both testes of healthy controls. Serum AMH was lower and FSH was higher in patients with monorchidism than in controls aged <3 and >13 years. Serum testosterone and LH did not differ significantly between patients and controls. CONCLUSION: In boys and adolescents with monorchidism, there is a dissociated capacity of the remaining testis to compensate for the absence of the other gonad: while Leydig cell function is largely compensated, Sertoli cell proliferation and function was lower than in controls.

A systems-based investigation into vitamin D and skeletal muscle repair, regeneration, and hypertrophy.

Skeletal muscle is a direct target for vitamin D. Observational studies suggest that low 25[OH]D correlates with functional recovery of skeletal muscle following eccentric contractions in humans and crush injury in rats. However, a definitive association is yet to be established. To address this gap in knowledge in relation to damage repair, a randomised, placebo-controlled trial was performed in 20 males with insufficient concentrations of serum 25(OH)D (45 ± 25 nmol/l). Prior to and following 6 wk of supplemental vitamin D3 (4,000 IU/day) or placebo (50 mg of cellulose), participants performed 20 × 10 damaging eccentric contractions of the knee extensors, with peak torque measured over the following 7 days of recovery. Parallel experimentation using isolated human skeletal muscle-derived myoblast cells from biopsies of 14 males with low serum 25(OH)D (37 ± 11 nmol/l) were subjected to mechanical wound injury, which enabled corresponding in vitro studies of muscle repair, regeneration, and hypertrophy in the presence and absence of 10 or 100 nmol 1α,25(OH)2D3. Supplemental vitamin D3 increased serum 25(OH)D and improved recovery of peak torque at 48 h and 7 days postexercise. In vitro, 10 nmol 1α,25(OH)2D3 improved muscle cell migration dynamics and resulted in improved myotube fusion/differentiation at the biochemical, morphological, and molecular level together with increased myotube hypertrophy at 7 and 10 days postdamage. Together, these preliminary data are the first to characterize a role for vitamin D in human skeletal muscle regeneration and suggest that maintaining serum 25(OH)D may be beneficial for enhancing reparative processes and potentially for facilitating subsequent hypertrophy.

Kocher-Debré-Semelaigne syndrome with rhabdomyolysis and increased creatinine.

Association of Kocher-Debré-Semelaigne syndrome-a myopathy of hypothyroidism in childhood characterized by muscular hypertrophy, with rhabdomyolysis is very rare. We present a case of Kocher-Debré-Semelaigne syndrome with rhabdomyolysis secondary to Hashimoto's thyroiditis. He had muscular symptoms simulating poly/dermatomyositis, massively elevated creatine kinase (CK) levels and high creatinine levels. All of the findings reversed on treatment of hypothyroidism. The response to the therapy strongly suggested that Kocher-Debré-Semelaigne (KDS) syndrome was the underlying etiology. Serum thyroid- stimulating hormone levels should be routinely determined in all patients with muscular symptoms and/or elevation of CK and creatinine, keeping KDS syndrome in mind.