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Myers, Kasiani C., Sonata Jodele, Adam S. Nelson, Erica Goodridge, Parinda A. Mehta, Robin Mueller, Christopher E. Dandoy, Adam Lane, Javier A. El-Bietar, and Stella M. Davies. "Transplant Associated Thrombotic Microangiopathy in Individuals with Fanconi Anemia." Blood 128, no. 22 (December 2, 2016): 2217. http://dx.doi.org/10.1182/blood.v128.22.2217.2217.
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Abstract Objective: Transplant-associated thrombotic microangiopathy (TA-TMA) is an increasingly recognized complication of hematopoietic stem cell transplantation (HSCT) due to vascular endothelial injury. TA-TMA most commonly affects the kidneys resulting in proteinuria, hypertension and often progresses to multi-organ failure in severe cases. We previously identified in our institutional prospective study of TA-TMA a higher incidence of TA-TMA in Fanconi anemia (FA) individuals. We hypothesized that exposure to cyclosporine (CSA), which has been implicated in TA-TMA, may have led to this increase. The goal of our current study was to examine the TA-TMA incidence in FA individuals undergoing HSCT with CSA exposure at our institution and its impact on transplant related morbidity and organ function. Methods: We performed a retrospective chart review in all patients with FA undergoing first unrelated donor T-depleted HSCT (2010-2016) using a busulfan, fludarabine, cyclophosphamide and ATG preparative regimen to identify the incidence of transplant-associated TMA and clinical outcomes. Subjects were stratified by cyclosporine use. Results: Forty-two patients underwent unrelated donor t-depleted HSCT using busulfan, fludarabine, cyclophosphamide and ATG during the study period. Additional GVHD prophylaxis with cyclosporine (CSA) was used in the first 29 subjects while subsequent subjects received no additional prophylaxis (n= 13). Incidence of TA-TMA in the CSA and Non-CSA groups was 66% (n=19/29) and 54% (n=7/13) respectively (p=0.51) and was increased from the overall institutional TA-TMA incidence of 34% (p=0.0011). Risk factors for severe TA-TMA were increased in the CSA-group with nephrotic range proteinuria in 53% compared with 14% of the non-CSA group in tested patients and increased complement activation by sC5b-9 levels 100% vs 20%. Median duration of active TA-TMA was longer in the CSA-group at 85 days compared with 41 in the non-CSA group. Complications of TA-TMA including hypertension, kidney injury, dialysis, pericardial effusion and pulmonary hypertension were all increased in the CSA group compared to the non-CSA group. Conclusion: Incidence of TA-TMA after HSCT is increased in FA compared to other HSCT recipients. Individuals receiving cyclosporine for GVHD prophylaxis had more severe TA-TMA than those who did not receive it, affecting transplant related morbidity and long-term renal function. Increased incidence of TA-TMA in individuals with FA may point to novel mechanisms of vascular endothelial injury. Better understanding of these mechanisms may allow for improved transplant risk stratification or new therapeutic approaches in solid tumor therapy. Disclosures Davies: Novartis: Honoraria.
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Zheng, Weiyan, Yi Luo, Yamin Tan, Jingsong He, Jimin Shi, Guoqin Wei, Jie Sun, et al. "Evaluation the Risk Factor of Transplantation-Associated Thrombotic Microangiopathy." Blood 116, no. 21 (November 19, 2010): 4527. http://dx.doi.org/10.1182/blood.v116.21.4527.4527.
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Abstract Abstract 4527 Background: Transplantation-associated thrombotic microangiopathy (TA-TMA) is lifethrewten though rare complication of allogeneic hematopoietic stem cell transplantation (HSCT). Diagnosis of TA-TMA is difficult due to its variation of criteria. Recently two new diagnositic criteria for TA-TMA have recently been proposed: the Bone Marrow Transplant Clinical Trials Network (BMTCTN) and the International Working Group (IWG) criteria. Our purpose is to investigate the indence and risk facter of TA-TMA in our institute. Study design and methods: All 8 cases of TA-TMA previously diagnosed at our institution between October 2005 and August 2010 were retrospectively evaluated and analysised. Table I showed the transplant details and patients characteristics. Results: Six patients performed Matched Unrelated Donor HSCT, two were haploidentical donor HSCT. Four patients complicated with hypohepatia, but only three patients had renal insufficient. The incidence of central nervous symptom abnormalities or dysfunction was very high (sever of eight patients). Four of eight patients were CSA linked TA-TMA, withdrawing CSA resulted in complete response. The other four patients were no CSA linked TA-TMA and developed aGVHD or CMV infection before TA-TMA. They had badly response to common treatment including plasma exchange (PE), steroid treatment and immunosuppression decreased. All of them died of multiple organ failure. Table II showed TA-TMA manifestations and associated circumstance of the patient. Conclusion: Our experience suggests that CSA linked TA-TMA is totally different from no CSA linked TA-TMA. The former had good response and prognosis, the later were always associated with GVHD, hypohepatia and virus infectious. The mortality of no CSA linked TA-TMA is high, they had poor prognosis and badly response. Disclosures: No relevant conflicts of interest to declare.
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Jadhav, Ashok, Venkat Gopalakrishnan, and Ahmed Shoker. "ComparativeIn VitroEffects of Calcineurin Inhibitors on Functional Vascular Relaxations of Both Rat Thoracic and Abdominal Aorta." Advances in Pharmacological Sciences 2013 (2013): 1–8. http://dx.doi.org/10.1155/2013/718313.
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Background and Aim. Calcineurin inhibitors (CNIs) have shown to develop hypertension in transplant patients. Thein vitroincubation effects of cyclosporine (CsA) and tacrolimus (Tac) on vascular relaxations of rat thoracic aorta (TA) and abdominal aorta (AA) need to be investigated.Methods. The optimal concentrations of CsA (1.0 mg/mL) and Tac (0.1 mg/mL) used to compare endothelium-dependent (acetylcholine (ACh)) and endothelium-independent (sodium nitroprusside (SNP)) vascular relaxation against the agonists in phenylephrine (PE-) constricted TA and AA of 13-week-old male Sprague Dawley rats (n=6).Results. In TA, the maximal vasodilator response elicited by ACh (control:Imax98%) was significantly (P<0.01) inhibited by CsA (Imax10%) but not by Tac (Imax97%). In AA, (control: IC5050 nM;Imax100%) CsA (IC507 μM; (P<0.01) showed strong sensitivity to inhibit ACh-dependent vascular relaxation than Tac (IC50215 nM (P<0.05);Imax98%). CsA and Tac failed to affect the inhibitory responses to SNP in both TA and AA.Conclusion. CsA exerts profound inhibitory effect on endothelium-dependent vasodilatation as compared to Tac in both TA and AA. Aortic rings from the thoracic region are more sensitive to CNIs, since the vasodilator response to ACh is solely mediated by NO while in the AA, ACh likely recruits other endothelial mediators besides NO to maintain vasodilatation.
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Krause Neto, Walter, and Eliane Florencio Gama. "STRENGTH TRAINING AND ANABOLIC STEROID DO NOT AFFECT MUSCLE CAPILLARIZATION OF MIDDLE-AGED RATS." Revista Brasileira de Medicina do Esporte 23, no. 2 (April 2017): 137–41. http://dx.doi.org/10.1590/1517-869220172302157902.
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ABSTRACT Introduction: It is generally accepted that the capillary network decreases with advancing age. The combined effect of resistance training (RT) and testosterone still needs to be elucidated. Objective: This study aimed to measure capillary profile of different skeletal muscles of middle-aged rats undergoing RT and administration of exogenous testosterone. Methods: Wistar rats were divided into five experimental groups: control with 13-month-old rats (SC), control with 16-month-old rats (SE), aged rats + anabolic agent (SA), aged rats + RT (T), and aged rats + RT + anabolic agent (TA). Results: For soleus, the SE group presented a decrease in the percentage of capillaries in comparison to SC group. SA, T, and TA groups had increased capillary volume in comparison to SC. As for the extensor digitorum longus (EDL), SA, T, and TA groups demonstrated lower capillary volume and numeric density in comparison to SC and SE. The EDL of the T and TA groups presented 70% less capillaries than soleus. The numerical and volumetric density and capillary ratio by muscle fiber were not statistically altered by any intervention. The cross-sectional area (CSA) of the soleus of the SA, T and TA groups was statistically different from SC group. The soleus CSA was greater in the TA and T groups than in the SC, SE and SA groups, and the EDL CSA was greater in the TA compared to all other groups. The TA group had greater values than the SE, SA, and T groups. Conclusion: The type of intervention used did not affect any variables measured in the capillary profile. However, the use of anabolic steroid and/or RT showed a tendency to decrease the density of capillaries in the EDL.
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Allen, Matti D., Brendan Major, Kurt Kimpinski, Timothy J. Doherty, and Charles L. Rice. "Skeletal muscle morphology and contractile function in relation to muscle denervation in diabetic neuropathy." Journal of Applied Physiology 116, no. 5 (March 1, 2014): 545–52. http://dx.doi.org/10.1152/japplphysiol.01139.2013.
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The objective of the study was to assess the effects of diabetic polyneuropathy (DPN) on muscle contractile properties in humans, and how these changes are related to alterations in muscle morphology and denervation. Patients with DPN ( n = 12) were compared with age- and sex-matched controls ( n = 12). Evoked and voluntary contractile properties, including stimulated twitch responses and maximal voluntary contractions, of the dorsiflexor muscles were assessed using an isometric ankle dynamometer. Motor unit number estimates (MUNE) of the tibialis anterior (TA) were performed via quantitative electromyography and decomposition-enhanced spike-triggered averaging. Peak tibialis anterior (TA) cross-sectional area (CSA; cm2), and relative proportion of contractile to noncontractile tissue (%) was determined from magnetic resonance images. Patients with DPN demonstrated decreased strength (−35%) and slower (−45%) dorsiflexion contractile properties for both evoked and voluntary contractions ( P < 0.05). These findings were not accounted for by differences in voluntary activation ( P > 0.05) or antagonist coactivation ( P > 0.05). Additionally, patients with DPN were weaker when strength was normalized to TA total CSA (−30%; P < 0.05) or contractile tissue CSA (−26%; P < 0.05). In the DPN patient group, TA MUNEs were negatively related to both % noncontractile tissue ( P < 0.05; r = 0.72) and twitch half-relaxation time ( P < 0.05; r = 0.60), whereas no relationships were found between these variables in controls ( P > 0.05). We conclude that patients with DPN demonstrated reduced strength and muscle quality as well as contractile slowing. This process may contribute to muscle power loss and functional impairments reported in patients with DPN, beyond the loss of strength commonly observed.
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Shin, Youngju, So Young Ahn, and Soo-Kyung Bok. "Relationships Between Relative Ankle Muscle Ratios, Severity of Symptoms, and Radiologic Parameters in Adolescent Patients With Symptomatic Flexible Flat Feet." Annals of Rehabilitation Medicine 45, no. 2 (April 30, 2021): 123–30. http://dx.doi.org/10.5535/arm.20174.
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Objective To investigate differences in the relative sizes of the ankle-stabilizing muscles in individuals with versus without flexible flat feet and to determine predictors of symptom severity.Methods This cross-sectional study included 30 patients with symptomatic flexible flat feet and 24 normal controls. The following were evaluated: foot posture index, resting calcaneal stance position angle, radiographic findings (calcaneal pitch, Meary’s angle, talocalcaneal angle, talonavicular coverage angle [TNCA]), foot function index (FFI), and cross-sectional areas (CSA) of the tibialis anterior (TA), tibialis posterior (TP), and peroneus longus (PL) upon ultrasonographic examination. To address morphometric differences among participants, individual muscle measurements were normalized to proportions of total muscle CSA. Between-group differences were evaluated with independent t-tests. Correlations between muscle ratios, radiographic parameters, and FFI scores were investigated. Logistic regression analysis was performed to determine which parameters predicted severe symptoms.Results The relative size of the TP was significantly greater and those of the TA and PL were significantly smaller in patients with flat feet than in normal controls. Correlations were found among relative muscle CSA ratios, radiographic parameters, and FFI score. Linear regression analysis confirmed that the TNCA and the relative CSA of the PL were independent predictors of symptom severity.Conclusion This study found significant differences in the relative CSAs of the ankle muscles in patients with flexible flat feet versus individuals without flat feet; these differences were significantly correlated with anatomic abnormalities. Symptoms were more severe in patients with relatively greater forefoot abduction and relatively smaller PL.
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Grindeland, R. E., R. R. Roy, V. R. Edgerton, E. J. Grossman, V. R. Mukku, B. Jiang, D. J. Pierotti, and I. Rudolph. "Interactive effects of growth hormone and exercise on muscle mass in suspended rats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 267, no. 1 (July 1, 1994): R316—R322. http://dx.doi.org/10.1152/ajpregu.1994.267.1.r316.
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Measures to attenuate muscle atrophy in rats in response to stimulated microgravity [hindlimb suspension (HS)] have been only partially successful. In the present study, hypophysectomized rats were in HS for 7 days, and the effects of recombinant human growth hormone (GH), exercise (Ex), or GH+Ex on the weights, protein concentrations, and fiber cross-sectional areas (CSAs) of hindlimb muscles were determined. The weights of four extensor muscles, i.e., the soleus (Sol), medial (MG) and lateral (LG) gastrocnemius, and plantaris (Plt), and one adductor, i.e., the adductor longus (AL), were decreased by 10-22% after HS. Fiber CSAs were decreased by 34% in the Sol and by 17% in the MG after HS. In contrast, two flexors, i.e., the tibialis anterior (TA) and extensor digitorum longus (EDL), did not atrophy. In HS rats, GH treatment alone maintained the weights of the fast extensors (MG, LG, Plt) and flexors (TA, EDL) at or above those of control rats. This effect was not observed in the slow extensor (Sol) or AL. Exercise had no significant effect on the weight of any muscle in HS rats. A combination of GH and Ex treatments yielded a significant increase in the weights of the fast extensors and in the CSA of both fast and slow fibers of the MG and significantly increased Sol weight and CSA of the slow fibers of the Sol. The AL was not responsive to either GH or Ex treatments. Protein concentrations of the Sol and MG were higher only in the Sol of Ex and GH + Ex rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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Bhatla, D., Stella M. Davies, R. E. Harris, M. Crockett, L. Shoultz, S. Shenoy, J. Bleesing, et al. "Reduced Intensity Conditioning Is Safe and Effective for Transplantation of Patients with Shwachman Diamond Syndrome." Blood 110, no. 11 (November 16, 2007): 2004. http://dx.doi.org/10.1182/blood.v110.11.2004.2004.
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Abstract Allogeneic hematopoietic stem cell transplantation is the only potentially curative treatment for the bone marrow dysfunction seen in patients with Shwachman-Diamond Syndrome (SDS). Historically, these patients have fared poorly with intensive conditioning regimens with increased regimen-related toxicity especially involving the heart and lungs. We report our institutional experience with a reduced intensity conditioning protocol in 7 patients with SDS and bone marrow aplasia or MDS/AML. Patient demographics are summarized in Table 1 below. The preparative regimen consisted of Campath-1H for 4 successive days (day -22 to day -19), Fludarabine 30 mg/m2/day for 5 days (Day - 8 to day -4) followed by Melphalan 140 mg/m2 for 1 day (day -3). Four patients received matched related marrow, 2 received matched unrelated peripheral blood stem cells (PBSC) and 1 received matched unrelated marrow. All but one were 8/8 allele HLA matched. Graft-versus-host disease (GVHD) prophylaxis consisted of Cyclosporine(CSA) and Methotrexate in all except one patient who received tacrolimus and mycophenolate mofetil as she was CSA intolerant. All patients established 100% donor-derived hematopoiesis. No major regimen related toxicity was seen except hyperglycemia requiring insulin in one patient and Grade II renal insufficiency in 1 patient which resolved with conservative management. Transplant outcomes are described in Table 2. These data indicate that HSCT with reduced intensity conditioning is feasible in patients with SDS and associated with excellent hematopoietic recovery and modest morbidity. Table 1. Patient Demographics Patients #1 #2 #3 #4 #5 #6 #7 Age(yrs) 8 10 12 6 3 29 1 Gender Male Male Male Male Male Female Female SBDS mutation 183_184 TA to CT 183_184 TA to CT K62X 183_184 TA to CT 183_184 TA to CT IVS2+2 T to C 183_184 TA to CT Clinical status Transfusion dependence, recurrent infections Cytopenias Cytopenias Dysplasia Cytopenias Acute myeloid leukemia Dysplasia, Cytopenias Marrow cytogenetics del20q12 and del7q31 i(7)(q10) del20q12 del20q12 del20q12 Complex karyotype including monosomy 7,del5q Normal Table 2. Transplant outcomes Patients Patients #1 #2 #3 #4 #5 #6 #7 Days to myeloid engraftment 15 12 15 11 14 14 13 Platelet Recovery(days) 27 39 33 18 68 14 not engrafted Donor Chimerism 100% 100% 100% 100% 100% 99.8% 100% Hospital stay(days) 29 32 35 28 29 22 46 Length of follow-up(days) 758 723 679 385 218 65 33 Acute GVHD Gd II skin None None None None Gd I skin None Lansky scale 100% 100% 100% 100% 100% 90% 60%
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Murphy, Kate T., Andrew M. Allen, Annabel Chee, Timur Naim, and Gordon S. Lynch. "Disruption of muscle renin-angiotensin system in AT1a−/−mice enhances muscle function despite reducing muscle mass but compromises repair after injury." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 303, no. 3 (August 1, 2012): R321—R331. http://dx.doi.org/10.1152/ajpregu.00007.2012.
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The role of the renin-angiotensin system (RAS) in vasoregulation is well established, but a localized RAS exists in multiple tissues and exerts diverse functions including autonomic control and thermogenesis. The role of the RAS in the maintenance and function of skeletal muscle is not well understood, especially the role of angiotensin peptides, which appear to contribute to muscle atrophy. We tested the hypothesis that mice lacking the angiotensin type 1A receptor (AT1A−/−) would exhibit enhanced whole body and skeletal muscle function and improved regeneration after severe injury. Despite 18- to 20-wk-old AT1A−/−mice exhibiting reduced muscle mass compared with controls ( P < 0.05), the tibialis anterior (TA) muscles produced a 25% higher maximum specific (normalized) force ( P < 0.05). Average fiber cross-sectional area (CSA) and fiber oxidative capacity was not different between groups, but TA muscles from AT1A−/−mice had a reduced number of muscle fibers as well as a higher proportion of type IIx/b fibers and a lower proportion of type IIa fibers ( P < 0.05). Measures of whole body function (grip strength, rotarod performance, locomotor activity) were all improved in AT1A−/−mice ( P < 0.05). Surprisingly, the recovery of muscle mass and fiber CSA following myotoxic injury was impaired in AT1A−/−mice, in part by impaired myoblast fusion, prolonged collagen infiltration and inflammation, and delayed expression of myogenic regulatory factors. The findings support the therapeutic potential of RAS inhibition for enhancing whole body and skeletal muscle function, but they also reveal the importance of RAS signaling in the maintenance of muscle mass and for normal fiber repair after injury.
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Jiang, B., Y. Ohira, R. R. Roy, Q. Nguyen, E. I. Ilyina-Kakueva, V. Oganov, and V. R. Edgerton. "Adaptation of fibers in fast-twitch muscles of rats to spaceflight and hindlimb suspension." Journal of Applied Physiology 73, no. 2 (August 1, 1992): S58—S65. http://dx.doi.org/10.1152/jappl.1992.73.2.s58.
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The adaptation of single fibers in medial gastrocnemius (MG), a fast-twitch extensor, and tibialis anterior (TA), a fast-twitch flexor, was studied after 14 days of spaceflight (COSMOS 2044) or hindlimb suspension. Cross-sectional area (CSA) and succinate dehydrogenase (SDH), alpha-glycerophosphate dehydrogenase (GPD), and myofibrillar adenosinetriphosphatase (ATPase) activities were determined in fibers identified in frozen serial cross sections. Fibers were categorized as light, dark, or intermediate on the basis of myosin ATPase staining and alkaline preincubation and immunohistochemically as reacting with slow, fast, or both slow and fast myosin heavy chain monoclonal antibodies. Because there was a close relationship between these two means of categorizing fibers, all fibers were categorized on the basis of the immunohistochemical reaction. The percentage of slow- and fast-twitch fibers of the MG and TA were unchanged in either group. Mean fiber size of all fibers, irrespective of type, was unaffected in either muscle after flight or suspension. The fibers that expressed both fast and slow myosin heavy chains were smaller than control in the MG of both experimental groups. Compared with control, the SDH and total SDH activities in the MG were significantly less in suspended rats, with the fast-twitch fibers showing the largest difference. The ATPase activity in the MG was higher in flight than in control or suspended rats. There were no significant effects of flight on fibers of the TA. In contrast, the TA in suspended rats had higher GPD activities than either control or flight rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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Antunes, Larissa, André Katayama Yamada, and Adriana Pertille. "EFFECTS OF BETA-HYDROXY-BETA-METHYL BUTYRATE IN MUSCLE REGENERATION OF RATS." Revista Brasileira de Medicina do Esporte 24, no. 2 (March 2018): 112–16. http://dx.doi.org/10.1590/1517-869220182402181184.
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ABSTRACT Introduction: Studies have shown that beta-hydroxy-beta-methyl butyrate (HMB) supplementation increases muscle strength and mass. Objective: To evaluate the effect of HMB supplementation on the muscle regeneration process in young and sedentary rats. Methods: Twenty-four male Wistar rats two months old were divided into two groups: lesion (LE) and supplemented (S), and evaluated in two moments - seven days (LE7; S7, n=6) and 21 days (LE21; S21, n=6). The right tibialis anterior muscle was subjected to cryolesion in all animals. After the injury, the LE group remained in the vivarium without any intervention. Group S received HMB calcium supplementation diluted in water by gavage (320 mg/kg/weight per day). The injury tibialis anterior (ITA), the tibialis anterior (TA), and the left soleus (SOL) muscles were removed, weighted and divided transversally into two parts, one for the analysis of the cross-sectional area (CSA) and the area of inflammation/regeneration and the other part to measure the muscular glycogen concentration. Data were evaluated using the SAS program considering mean and standard deviation. For analysis of variance the ANOVA test was used followed by the Tukey-HSD test (p≤0.05). Results: The ITA muscle weight was higher in S21 compared to S7 (p<0.05). The groups LE21 and S21 presented greater CSA of muscle fibers area and smaller ITA regeneration/inflammation area (p<0.05) when compared with the LE7 and S7 groups. There was an increase in muscle glycogen levels in S7 group compared to LE7 and S21 groups for TA and SOL (p<0.01), as well as in S21 group compared to LE21 for SOL (p<0.05). Conclusion: HMB did not influence the muscle regeneration process and did not favor anabolic activity in the different muscular fibers of young sedentary rats. Level of Evidence II; Therapeutic studies - Investigation of treatment results.
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DeChick, Auryana, Rebecca Hetz, Jack Lee, and Diana L. Speelman. "Increased Skeletal Muscle Fiber Cross-Sectional Area, Muscle Phenotype Shift, and Altered Insulin Signaling in Rat Hindlimb Muscles in a Prenatally Androgenized Rat Model for Polycystic Ovary Syndrome." International Journal of Molecular Sciences 21, no. 21 (October 25, 2020): 7918. http://dx.doi.org/10.3390/ijms21217918.
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Women with polycystic ovary syndrome (PCOS) are reported to have greater lean mass and insulin resistance. To examine muscular changes in a prenatally androgenized (PNA) rat model for PCOS, Sprague–Dawley rats were exposed to 5 mg testosterone or vehicle daily on gestational days 16–19. At 15 weeks of age, endurance on a rota-rod treadmill was measured. At 16 weeks of age, fasting blood glucose and insulin, hindlimb skeletal muscle mass, muscle fiber cross-sectional area (CSA) and composition, and intra- and peri-muscular lipid droplets were examined. Expression of mitochondrial marker ATP synthase and insulin signaling proteins were also investigated. Compared with controls, PNA female rats demonstrated greater total body and hindlimb muscle weights, greater muscle fiber CSA, and trending reduced time on the rota-rod. An increase in fibers co-expressing the slow and fast isoforms of myosin (90 vs. 86%, p < 0.05) and greater expression of ATP synthase (6-fold, p < 0.005) were observed in the gastrocnemius (GN) muscle. More lipid content was observed in GN and tibialis anterior (TA) muscles. PNA rats had elevated fasting serum insulin (1.9 vs. 1.2 ng/mL, p < 0.005) but comparable fasting glucose. Expression of total and Ser636/9-phosphorylated IRS1 were altered in PNA rat hindlimb muscles. Together, skeletal muscle alterations in hindlimb muscles of a PNA rat model for PCOS may represent consequences of, or adaptations to, insulin resistance in this model.
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Ark, R., and M. Bukhari. "POS0511 USING HIP STRUCTURAL ANALYSIS MEASUREMENTS TO PREDICT FRACTURE IN RHEUMATOID ARTHRITIS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 488.2–489. http://dx.doi.org/10.1136/annrheumdis-2021-eular.802.
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Background:Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease and increases the risk of developing osteoporosis. Incidence of fracture is higher in this group of patients compared to the general population and can lead to increased morbidity (1). Bone strength of the proximal femur is not only linked to bone mineral density; it also depends on the geometric properties of the bone mass (2). Hip structural analysis (HSA) is a technique used to assess hip bone structure that takes geometric measurements of the femur from dual-energy X-ray absorptiometry (DEXA) images (3).Objectives:To determine whether HSA measurements help predict fracture in patients with RA.Methods:Data were collected from June 2004 to August 2017 from RA patients who underwent a DEXA scan at a District General Hospital. This included hip axis length (HAL), cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), distance from centre of femoral head to centre of femoral neck (D1) and to inter-trochanteric line (D2), mean femoral neck diameter (D3), shaft angle (A) neck/shaft angle (Θ) and proximal femur strength index (SI) and distance from centre of mass of femoral neck to superior neck margin (Y). Fracture was predicted by a series of binomial logistic regression models, adjusted for sex, age and bone mineral density (BMD). Odds ratios with 95% confidence intervals and area under the receiver operating characteristic curve (AUC) were calculated.Results:2077 patients with RA were identified, 1632 were female and the mean age was 66.7. HAL, D1, D2, D3, A, Θ and Y were not significant predictors of fracture in regression models; odds ratios are included in table 1. CSA, CSMI and SI predicted fracture risk. The AUC for CSA, CSMI and SI regression models were 0.632, 0.609 and 0.625 respectively.Table 1.Odds ratios of fracture for different HSA parameters in RA patientsHSA ParameterOdds Ratio (95% Confidence Interval)HAL1.01410 (0.99958 - 1.02883)CSMI0.99994 (0.99990 - 0.99998)CSA0.98523 (0.98065 - 0.98982)D11.01683 (0.98925 - 1.04518)D21.01286 (0.99886 - 1.02705)D31.00664 (0.96958 - 1.04511)Y1.04580 (0.98633 - 1.10886)A1.00898 (0.98878 - 1.02959)Θ1.00276 (0.98672 - 1.01906)SI0.56769 (0.43400 - 0.74258)Figure 1.Receiver operating characteristic curves for CSA (red), CSMI (green) and SI (blue). AUC for CSA was 0.632, CSMI-0.609 and SI-0.625.Conclusion:These data suggest that CSA, CSMI and SI help predict the fracture risk in patients with RA. HAL, D1, D2, D3, A, Θ and Y do not predict risk of fracture. The CSA regression model was the strongest predictor of fracture. HSA measurements can therefore help predict risk of fracture in conjunction with other factors. Limitations of the study are that it was retrospective and only studied patients who had a DEXA scan.References:[1]Xue A, Wu S, Jiang L, Feng A, Guo H, Zhao P. Bone fracture risk in patients with rheumatoid arthritis: A meta-analysis. Medicine. 2017; 96 (36): e6983. Available from: doi: 10.1097/MD.0000000000006983.[2]Faulkner KG, Wacker WK, Barden HS, Simonelli C, Burke PK, Ragi S, Del Rio L. Femur strength index predicts hip fracture independent of bone density and hip axis length. Osteoporos Int. 2006;17(4):593-9. doi: 10.1007/s00198-005-0019-4.[3]Kaptoge S, Beck TJ, Reeve J, Stone KL, Hillier TA, Cauley JA, et al. Prediction of Incident Hip Fracture Risk by Femur Geometry Variables Measured by Hip Structural Analysis in the Study of Osteoporotic Fractures. Journal of Bone and Mineral Research. 2008; 23 (12): 1892-1904. Available from: doi: https://doi.org/10.1359/jbmr.080802.Disclosure of Interests:None declared
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Khandavilli, U. B. Rao, Leila Keshavarz, Eliška Skořepová, René R. E. Steendam, and Patrick J. Frawley. "Organic Salts of Pharmaceutical Impurity p-Aminophenol." Molecules 25, no. 8 (April 21, 2020): 1910. http://dx.doi.org/10.3390/molecules25081910.
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The presence of impurities can drastically affect the efficacy and safety of pharmaceutical entities. p-Aminophenol (PAP) is one of the main impurities of paracetamol (PA) that can potentially show toxic effects such as maternal toxicity and nephrotoxicity. The removal of PAP from PA is challenging and difficult to achieve through regular crystallization approaches. In this regard, we report four new salts of PAP with salicylic acid (SA), oxalic acid (OX), l-tartaric acid (TA), and (1S)-(+)-10-camphorsulfonic acid (CSA). All the PAP salts were analyzed using single-crystal X-ray diffraction, powder X-ray diffraction, infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. The presence of minute amounts of PAP in paracetamol solids gives a dark color to the product that was difficult to remove through crystallization. In our study, we found that the addition of small quantities of the aforementioned acids helps to remove PAP from PA during the filtration and washings. This shows that salt formation could be used to efficiently remove challenging impurities.
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Ark, R., and M. Bukhari. "AB0607 DO HIP STRUCTURAL ANALYSIS MEASUREMENTS PREDICT FRACTURE RISK IN PATIENTS WITH POLYMYALGIA RHEUMATICA?" Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1339.2–1339. http://dx.doi.org/10.1136/annrheumdis-2021-eular.337.
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Background:Polymyalgia Rheumatica (PMR) is an inflammatory condition which commonly affects the elderly. Risk of fracture is higher in this group of patients compared to the general population and can lead to increased morbidity and mortality (1). Hip structural analysis (HSA) is a technique that uses dual-energy X-ray absorptiometry (DEXA) images to assess hip bone structure (2).Objectives:To identify whether HSA measurements help predict fracture in patients with PMR.Methods:Data were collected from June 2004 to October 2010 from PMR patients who had a DEXA scan at a District General Hospital. This included hip axis length (HAL), cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), distance from centre of femoral head to centre of femoral neck (D1) and to inter-trochanteric line (D2), mean femoral neck diameter (D3), shaft angle (A) neck/shaft angle (Θ) and proximal femur strength index (SI) and distance from centre of mass of femoral neck to superior neck margin (Y). Fracture was predicted by a series of binomial logistic regression models, adjusted for age and sex. Odds ratios with 95% confidence intervals and area under the receiver operating characteristic curve (AUC) were calculated.Results:714 patients with PMR were identified, 182 were male and the mean age was 70.5. HAL, CSMI, D1, D2, D3, A, Θ, SI and Y were not significant predictors of fracture in regression models; odds ratios are included in Table 1. CSA predicted fracture risk; odds ratio was 0.988 with a 95% confidence interval of 0.980-0.997. The AUC for the CSA regression model was 0.6739.Table 1.Odds ratios of fracture for different HSA parametersHSA ParameterOdds Ratio (95% confidence interval)HAL1.008 (0.982 - 1.035)CSMI1.000 (0.999 - 1.000)CSA0.988 (0.980 - 0.997)D11.029 (0.972 - 1.089)D21.010 (0.981 - 1.040)D31.033 (0.962 - 1.109)Y1.087 (0.966 - 1.223)A0.983 (0.940 - 1.029)Θ1.007 (0.975 - 1.039)SI0.683 (0.406 - 1.150)Conclusion:These data suggest that CSA helps predict the risk of fracture in patients with PMR. HAL, CSMI, D1, D2, D3, A, Θ, SI and Y do not predict fracture risk. Limitations of the study are that it was retrospective and only studied patients who underwent DEXA scans. The study may have been underpowered to detect the impact of some HSA measurements on fracture risk.References:[1]Chatzigeorgiou C, Mackie SL. Comorbidity in polymyalgia rheumatica. Reumatismo. 2018; 70 1:35-43. Available from: http://eprints.whiterose.ac.uk/132109/\\.[2]Kaptoge S, Beck TJ, Reeve J, Stone KL, Hillier TA, Cauley JA, et al. Prediction of Incident Hip Fracture Risk by Femur Geometry Variables Measured by Hip Structural Analysis in the Study of Osteoporotic Fractures. Journal of Bone and Mineral Research. 2008; 23 (12): 1892-1904. Available from: doi: https://doi.org/10.1359/jbmr.080802Disclosure of Interests:None declared.
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Totosy de Zepetnek, J. E., H. V. Zung, S. Erdebil, and T. Gordon. "Innervation ratio is an important determinant of force in normal and reinnervated rat tibialis anterior muscles." Journal of Neurophysiology 67, no. 5 (May 1, 1992): 1385–403. http://dx.doi.org/10.1152/jn.1992.67.5.1385.
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1. The technique of glycogen depletion and periodic acid-Schiff (PAS) staining, which identifies glycogen-free muscle fibers, was used to directly count the number (N) and measure the cross-sectional area (CSA) of muscle fibers in single motor units (MUs) from normal and reinnervated tibialis anterior (TA) muscles. Indirect estimates, derived from the proportions of muscle fiber types to MU types, were also made, and force per unit area (or specific force, SF) was calculated. Previous results using direct and indirect approaches have been contradictory. To shed more light on this issue, the relative contributions of N, mean fiber area (A), and SF to muscle-unit force were determined by the use of both methods. 2. TA muscles were examined in experimental rats 3.5-10 mo after cutting and resuturing the common peroneal nerve in one hindlimb and in muscles in age-matched control rats. Ventral roots were dissected to isolate and characterize single MUs according to contraction speed, sag, and fatigability. One unit per muscle was selected for repetitive tetanic stimulation designed to deplete muscle fiber glycogen stores. Muscles were removed for identification of the unit with the PAS reaction and histochemical fiber typing by the use of modified standard techniques. 3. In the total population of MUs sampled, isometric tetanic force ranged from 5 to 441 mN in normal muscles and from 5 to 498 mN in reinnervated muscles, and the mean values were not significantly different. In the smaller sample of glycogen-depleted units from normal muscle, for a force range of 14-217 mN, N varied from 57 to 202, and A varied from 1,135 +/- 45 to 6,706 +/- 172 (SE) microns2. Within each unit the variation in fiber area is broad. After reinnervation, for a force range of 30-278 mN, N varied from 70 to 374, and A varied from 1,694 +/- 81 to 5,425 +/- 93 microns2. Mean fiber number was 153 +/- 18 in reinnervated muscle, which is significantly higher (P less than 0.01) than the normal value of 121 +/- 9. 4. The contribution of N and A to MU tetanic force was assessed by plotting each factor as a function of force on a log-log scale. N accounts for 39% and A for 49% of the variation in force in normal muscle. The contributions are changed after reinnervation where N, accounting for 65% of force, appears to compensate for the reduced range in A, which accounts for only 19% of the variation in force.(ABSTRACT TRUNCATED AT 400 WORDS)
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梁, 敏. "Learning from Heterogeneous Temporal Da-ta Based on Electronic Health Records." Computer Science and Application 10, no. 01 (2020): 1–10. http://dx.doi.org/10.12677/csa.2020.101001.
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KRISTEK, F., M. DROBNA, and S. CACANYIOVA. "Different Structural Alterations in Individual Conduit Arteries of SHRs Compared to Wistar Rats From the Prehypertensive Period to Late Adulthood." Physiological Research, October 17, 2017, 769–80. http://dx.doi.org/10.33549/physiolres.933690.
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Structural changes of thoracic aorta (TA), carotid (CA) and iliac artery (IA) were assessed in Wistar and spontaneously hypertensive rats (SHR) aged 3, 17, and 52 weeks. Systolic blood pressure (sBP) was measured by plethysmography weekly. After perfusion fixation the arteries were processed for electron microscopy. The wall thickness (WT), cross-sectional area (CSA), inner diameter (ID), and WT/ID in all arteries and volume densities of endothelial cells (ECs), muscle cells (SMCs), and extracellular matrix (ECM) in TA were measured and their CSAs were calculated. In 3-week-old SHR compared to Wistar rats, sBP did not differ; in the TA, all parameters (WT, CSA, ID, WT/ID, CSA of SMCs, CSA of ECs, and CSA of ECM) were decreased; in CA, WT and CSA did not differ, ID was decreased, and WT/ID was increased; in IA, WT, CSA, and ID were increased. In 17- and 52-week-old SHRs, sBP and all parameters in all arteries were increased, only ID in IE in 52-week-old SHRs and CSA of ECs in the TA in 17-week-old SHRs did not change. Disproportionality between BP increase and structural alterations during ontogeny in SHR could reflect the flexibility of the arterial tree to the different needs of supplied areas.
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WENS, I., U. DALGAS, K. VERBOVEN, L. KOSTEN, A. STEVENS, N. HENS, and B. O. EIJNDE. "Impact of High Intensity Exercise on Muscle Morphology in EAE Rats." Physiological Research, December 13, 2015, 907–23. http://dx.doi.org/10.33549/physiolres.932824.
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The impact of high-intensity exercise on disease progression and muscle contractile properties in experimental autoimmune encephalomyelitis (EAE) remains unclear. Control (CON) and EAE rats were divided into sedentary and exercise groups. Before onset (experiment 1, n=40) and after hindquarter paralysis (experiment 2, n=40), isokinetic foot extensor strength, cross sectional area (CSA) of tibialis anterior (TA), extensor digitorum longus (EDL) and soleus (SOL) and brain-derived neurotrophic factor (BDNF) levels were assessed. EAE reduced muscle fiber CSA of TA, EDL and SOL. In general, exercise was not able to affect CSA, whereas it delayed hindquarter paralysis peak. CON muscle work peaked and declined, while it remained stable in EAE. BDNF-responses were not affected by EAE or exercise. In conclusion, EAE affected CSA-properties of TA, EDL and SOL, which could, partly, explain the absence of peak work during isokinetic muscle performance in EAE-animals. However, exercise was not able to prevent muscle fiber atrophy.
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Joleby, Malin, Carolina Lunde, Sara Landström, and Linda S. Jonsson. "“All of Me Is Completely Different”: Experiences and Consequences Among Victims of Technology-Assisted Child Sexual Abuse." Frontiers in Psychology 11 (December 7, 2020). http://dx.doi.org/10.3389/fpsyg.2020.606218.
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The aim of the present study was to gain a first-person perspective on the experiences of technology-assisted child sexual abuse (TA-CSA), and a deeper understanding of the way it may affect its victims. Seven young women (aged 17–24) with experience of TA-CSA before the age of 18 participated in individual in-depth interviews. The interviews were teller-focused with the aim of capturing the interviewee’s own story about how they made sense of their experiences over time, and what impact the victimization had on them in the short and long terms. Thematic analysis of the interviews revealed a broad range of abusive experiences that had profoundly impacted the individuals’ lives, health and self-concepts. Three dominant themes emerged from the analysis – From thrilling to abusive, Negative effect on health and wellbeing, and A new self after the abuse. From thrilling to abusive captures the wide range of experiences described, starting from the child’s own sexual curiosity to descriptions of having been manipulated or threatened into engaging in sexual activity, as well as the sometimes long and complex process of understanding the severity of one’s experiences. Negative effect on health and wellbeing describes the victimization’s comprehensive impact on the life and health of the participants, how they blamed themselves for what had happened, and the struggle of having to live with the constant fear of pictures from the abuse resurfacing. A new self after the abuse depicts how the victimization impacted the way participants viewed and thought about themselves in relation to others, and distorted their views of their bodies. The findings are discussed in relation to previous research on both offline CSA and TA-CSA, as well as theoretical and practical implications.
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Mayer, Kirby P., Melissa L. Thompson Bastin, Ashley A. Montgomery-Yates, Amy M. Pastva, Esther E. Dupont-Versteegden, Selina M. Parry, and Peter E. Morris. "Acute skeletal muscle wasting and dysfunction predict physical disability at hospital discharge in patients with critical illness." Critical Care 24, no. 1 (November 4, 2020). http://dx.doi.org/10.1186/s13054-020-03355-x.
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Abstract Background Patients surviving critical illness develop muscle weakness and impairments in physical function; however, the relationship between early skeletal muscle alterations and physical function at hospital discharge remains unclear. The primary purpose of this study was to determine whether changes in muscle size, strength and power assessed in the intensive care unit (ICU) predict physical function at hospital discharge. Methods Study design is a single-center, prospective, observational study in patients admitted to the medicine or cardiothoracic ICU with diagnosis of sepsis or acute respiratory failure. Rectus femoris (RF) and tibialis anterior (TA) muscle ultrasound images were obtained day one of ICU admission, repeated serially and assessed for muscle cross-sectional area (CSA), layer thickness (mT) and echointensity (EI). Muscle strength, as measured by Medical Research Council-sum score, and muscle power (lower-extremity leg press) were assessed prior to ICU discharge. Physical function was assessed with performance on 5-times sit-to-stand (5STS) at hospital discharge. Results Forty-one patients with median age of 61 years (IQR 55–68), 56% male and sequential organ failure assessment score of 8.1 ± 4.8 were enrolled. RF muscle CSA decreased significantly a median percent change of 18.5% from day 1 to 7 (F = 26.6, p = 0.0253). RF EI increased at a mean percent change of 10.5 ± 21% in the first 7 days (F = 3.28, p = 0.081). At hospital discharge 25.7% of patients (9/35) met criteria for ICU-acquired weakness. Change in RF EI in first 7 days of ICU admission and muscle power measured prior to ICU were strong predictors of ICU-AW at hospital discharge (AUC = 0.912). Muscle power at ICU discharge, age and ICU length of stay were predictive of performance on 5STS at hospital discharge. Conclusion ICU-assessed muscle alterations, specifically RF EI and muscle power, are predictors of diagnosis of ICU-AW and physical function assessed by 5x-STS at hospital discharge in patients surviving critical illness.