scholarly journals Inhibition of TNF-αReverses the Pathological Resorption Pit Profile of Osteoclasts from Patients with Acute Charcot Osteoarthropathy

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Nina L. Petrova ◽  
Peter K. Petrov ◽  
Michael E. Edmonds ◽  
Catherine M. Shanahan

We hypothesised that tumour necrosis factor-α(TNF-α) may enhance receptor activator of nuclear factor-κβligand- (RANKL-) mediated osteoclastogenesis in acute Charcot osteoarthropathy. Peripheral blood monocytes were isolated from 10 acute Charcot patients, 8 diabetic patients, and 9 healthy control subjects and culturedin vitroon plastic and bone discs. Osteoclast formation and resorption were assessed after treatment with (1) macrophage-colony stimulating factor (M-CSF) and RANKL and (2) M-CSF, RANKL, and neutralising antibody to TNF-α(anti-TNF-α). Resorption was measured on the surface of bone discs by image analysis and under the surface using surface profilometry. Although osteoclast formation was similar in M-CSF + RANKL-treated cultures between the groups (p>0.05), there was a significant increase in the area of resorption on the surface (p<0.01) and under the surface (p<0.01) in Charcot patients compared with diabetic patients and control subjects. The addition of anti-TNF-αresulted in a significant reduction in the area of resorption on the surface (p<0.05) and under the surface (p<0.05) only in Charcot patients as well as a normalisation of the aberrant erosion profile. We conclude that TNF-αmodulates RANKL-mediated osteoclastic resorptionin vitroin patients with acute Charcot osteoarthropathy.

1996 ◽  
Vol 91 (5) ◽  
pp. 559-565 ◽  
Author(s):  
Paetrick M. Netten ◽  
Hub Wollersheim ◽  
Theo Thien ◽  
Jos A. Lutterman

1. In the feet of patients with diabetic neuropathy, total skin blood flow is increased due to an increased shunt flow. The question is, does this increased anastomotic shunt flow lead to either under- or overperfused nutritive capillaries. 2. To solve this question, skin microcirculation tests of the left big toe were performed in 20 healthy control subjects and in 40 insulin-dependent diabetic patients without macroangiopathy, 20 without and 20 with neuropathy. Skin temperature measurements and laser Doppler fluxmetry were performed to record mainly shunt flow and capillaroscopy to study nailfold capillary blood flow. 3. The insulin-dependent diabetic patients with neuropathy had a higher baseline skin temperature (mean ± SEM; 30.0 ± 0.6°C) and laser Doppler fluxmetry [26.2 ± 2.2 perfusion units (pu)] than patients without neuropathy (27.2 ± 0.8°C, P < 0.01; 16.1 ± 2.0 pu, P < 0.01) and healthy control subjects (27.9 ± 0.7°C, P < 0.05; 18.6 ± 2.8 pu, P < 0.05). Sympathetic stimulation (inspiratory gasp) resulted in a smaller laser Doppler fluxmetry decrease in the neuropathic patients (31.4 ± 4.6%) compared with non-neuropathic patients (48.2 ± 5.1%, P < 0.05) and control subjects (49.0 ± 3.8%, P < 0.05), while no difference between the three groups was seen in the laser Doppler fluxmetry decrease during a postural vasoconstriction test. The number of visible capillaries was highest in the neuropathic patients (10.2 ± 0.6/0.5 mm2), when compared with non-neuropathic patients (8.7 ± 1.2/0.5 mm2, P < 0.05) and control subjects (8.3 ± 0.3/0.5 mm2, P < 0.001). Capillary blood-cell velocity was significantly higher in the neuropathic patients (0.32 ± 0.05 mm/s) compared with non-neuropathic patients (0.23 ± 0.03 mm/s, P < 0.05) and control subjects (0.23 ± 0.02 mm/s, P < 0.01). 4. We conclude that there is an overperfused nutritive capillary circulation in the feet of patients with diabetic neuropathy. This is in contradiction to the capillary steal phenomenon and favours the hyperdynamic hypothesis to explain the decreased healing potential in diabetic neuropathic foot ulceration.


1982 ◽  
Vol 48 (03) ◽  
pp. 289-293 ◽  
Author(s):  
B A van Oost ◽  
B F E Veldhuyzen ◽  
H C van Houwelingen ◽  
A P M Timmermans ◽  
J J Sixma

SummaryPlatelets tests, acute phase reactants and serum lipids were measured in patients with diabetes mellitus and patients with peripheral vascular disease. Patients frequently had abnormal platelet tests and significantly increased acute phase reactants and serum lipids, compared to young healthy control subjects. These differences were compared with multidiscriminant analysis. Patients could be separated in part from the control subjects with variables derived from the measurement of acute phase proteins and serum lipids. Platelet test results improved the separation between diabetics and control subjects, but not between patients with peripheral vascular disease and control subjects. Diabetic patients with severe retinopathy frequently had evidence of platelet activation. They also had increased acute phase reactants and serum lipids compared to diabetics with absent or nonproliferative retinopathy. In patients with peripheral vascular disease, only the fibrinogen concentration was related to the degree of vessel damage by arteriography.


2017 ◽  
Vol 23 (7) ◽  
pp. 577-583 ◽  
Author(s):  
Beatrice Frajo-Apor ◽  
Georg Kemmler ◽  
Silvia Pardeller ◽  
Markus Huber ◽  
Christian Macina ◽  
...  

AbstractObjectives:Social cognitive deficits have been discussed to be endophenotypes for schizophrenia and other serious mental illnesses. The current study aimed to assess emotional intelligence (EI) in unaffected siblings of schizophrenia patients to investigate its potential role as endophenotype for schizophrenia.Methods:EI was measured in 56 schizophrenia patients, 57 unaffected siblings, and 127 healthy control subjects by using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). In addition, non-social cognition was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS). Linear mixed models with compound symmetric correlation structure were used for of the three groups with respect to EI and non-social cognition.Results:Schizophrenia patients showed significantly lower overall EI and performed significantly worse in three out of four MSCEIT branches compared to unaffected siblings and control subjects, whereas the two latter groups had comparable EI levels. Similar performance patterns (patients<unaffected siblings=control subjects) were found with respect to non-social cognition. Solely in the “Tower of London” test, siblings achieved significantly lower task scores compared to control subjects.Conclusions:Based on our results, EI as measured with the MSCEIT does not seem to represent a marker of risk for schizophrenia. Further investigations should concentrate on other EI measures to reassess this finding. (JINS, 2017,23, 577–583)


1982 ◽  
Vol 156 (6) ◽  
pp. 1604-1614 ◽  
Author(s):  
E H Burger ◽  
J W Van der Meer ◽  
J S van de Gevel ◽  
J C Gribnau ◽  
G W Thesingh ◽  
...  

The origin of osteoclasts was studied in an in vitro model using organ cultures of periosteum-free embryonic mouse long-bone primordia, which were co-cultured with various cell populations. The bone rudiments were freed of their periosteum-perichondrium by collagenase treatment in a stage before cartilage erosion and osteoclast formation, and co-cultured for 7 d with either embryonic liver or mononuclear phagocytes from various sources. Light and electron microscopic examination of the cultures showed that mineralized matrix-resorbing osteoclasts developed only in bones co-cultured with embryonic liver or with cultured bone marrow mononuclear phagocytes but not when co-cultured with blood monocytes or resident or exudate peritoneal macrophages. Osteoclasts developed from the weakly adherent, but not from the strongly adherent cells of bone marrow cultures, whereas 1,000 rad irradiation destroyed the capacity of such cultures to form osteoclasts. In bone cultures to which no other cells were added, osteoclasts were virtually absent. Bone-resorbing activity of in vitro formed osteoclasts was demonstrated by 45Ca release studies. These studies demonstrate that osteoclasts develop from cells present in cultures of proliferating mononuclear phagocytes and that, at least in our system, monocytes and macrophages are unable to form osteoclasts. The most likely candidates for osteoclast precursor cells seem to be monoblasts and promonocytes.


2021 ◽  
Vol 12 ◽  
Author(s):  
Fuyao Yu ◽  
Bing He ◽  
Li Chen ◽  
Fengzhe Wang ◽  
Haidong Zhu ◽  
...  

ObjectiveSkeletal muscle fat content is one of the important contributors to insulin resistance (IR), but its diagnostic value remains unknown, especially in the Chinese population. Therefore, we aimed to analyze differences in skeletal muscle fat content and various functional MRI parameters between diabetic patients and control subjects to evaluate the early indicators of diabetes. In addition, we aimed to investigate the associations among skeletal muscle fat content, magnetic resonance parameters of skeletal muscle function and IR in type 2 diabetic patients and control subjects.MethodsWe enrolled 12 patients (age:29-38 years, BMI: 25-28 kg/m2) who were newly diagnosed with type 2 diabetes (intravenous plasma glucose concentration≥11.1mmol/l or fasting blood glucose concentration≥7.0mmol/l) together with 12 control subjects as the control group (age: 26-33 years, BMI: 21-28 kg/m2). Fasting blood samples were collected for the measurement of glucose, insulin, 2-hour postprandial blood glucose (PBG2h), and glycated hemoglobin (HbAlc). The magnetic resonance scan of the lower extremity and abdomen was performed, which can evaluate visceral fat content as well as skeletal muscle metabolism and function through transverse relaxation times (T2), fraction anisotropy (FA) and apparent diffusion coefficient (ADC) values.ResultsWe found a significant difference in intermuscular fat (IMAT) between the diabetes group and the control group (p&lt;0.05), the ratio of IMAT in thigh muscles of diabetes group was higher than that of control group. In the entire cohort, IMAT was positively correlated with HOMA-IR, HbAlc, T2, and FA, and the T2 value was correlated with HOMA-IR, PBG2h and HbAlc (p&lt;0.05). There were also significant differences in T2 and FA values between the diabetes group and the control group (p&lt;0.05). According to the ROC, assuming 8.85% of IMAT as the cutoff value, the sensitivity and specificity of IMAT were 100% and 83.3%, respectively. Assuming 39.25ms as the cutoff value, the sensitivity and specificity of T2 value were 66.7% and 91.7%, respectively. All the statistical analyses were adjusted for age, BMI and visceral fat content.ConclusionDeposition of IMAT in skeletal muscles seems to be an important determinant for IR in type 2 diabetes. The skeletal muscle IMAT value greater than 8.85% and the T2 value greater than 39.25ms are suggestive of IR.


Background: Adiponectin is a collagen-like plasma protein secreted by adipocytes that has been suggested to play a causal role in the development of insulin resistance. Even though hypoadiponectinaemia is reported to be closely associated with obesity-related diseases such as ACVD, type 2 DM, dyslipidaemia, report from our environment is lacking. Materials and Methods: Serum adiponectin, insulin and glucose were measured in 90 type 2 diabetic and control subjects respectively. The patients were known diabetics attending the diabetic clinic at the ABUTH, Zaria. The control subjects were apparently healthy individuals within the hospital and Zaria environs. Results: Mean serum adiponectin levels were significantly lower (P<0.05) in the diabetic patients than in the control subjects. On the other hand, the mean values of insulin and glucose were significantly higher (P<0.05) in the diabetic patients than in the controls. Conclusion: Measurement of serum adiponectin as an adjunct in the biochemical assessment of type 2 DM is suggested.


2019 ◽  
Vol 7 ◽  
pp. 205031211882341 ◽  
Author(s):  
Takuo Nomura ◽  
Tomoyasu Ishiguro ◽  
Masayoshi Ohira ◽  
Hiroyuki Oka ◽  
Yukio Ikeda

Objectives: To determine standard reference values for isometric knee extension force using a cohort of Japanese type 2 diabetic patients without diabetic polyneuropathy. Methods: Patient data were collected from the Multicenter Survey of the Isometric Lower Extremity Strength in Type 2 Diabetes study and compared with previously published data of healthy control subjects. In total, we enrolled 898 patients with type 2 diabetes aged 30–87 years, who did not have diabetic polyneuropathy. The control group included 510 healthy subjects aged 30–88 years. Maximum isometric knee extension force (KEF) values were obtained by using a hand-held dynamometer with belt stabilization. In addition, KEF (kgf) was adjusted for bodyweight (kg) to calculate %KEF. Results: KEF and %KEF decreased with age in both patients with diabetes and healthy control subjects. The mean values of KEF and %KEF in patients with diabetes were reduced by 9.7% and 20.8%, respectively, in males, and by 11.6% and 23.0%, respectively, in females compared to the values in healthy control subjects. Conclusion: KEF and %KEF in patients with type 2 diabetes without diabetic polyneuropathy may reduce by approximately 10% and 20%, respectively, compared to these values in healthy control subjects. This study provides reference values for isometric KEF with respect to sex in a population covering a wide age range.


2005 ◽  
Vol 50 (9) ◽  
pp. 525-533 ◽  
Author(s):  
Benoit Bediou ◽  
Pierre Krolak-Salmon ◽  
Mohamed Saoud ◽  
Marie-Anne Henaff ◽  
Michael Burt ◽  
...  

Background: Impaired facial expression recognition in schizophrenia patients contributes to abnormal social functioning and may predict functional outcome in these patients. Facial expression processing involves individual neural networks that have been shown to malfunction in schizophrenia. Whether these patients have a selective deficit in facial expression recognition or a more global impairment in face processing remains controversial. Objective: To investigate whether patients with schizophrenia exhibit a selective impairment in facial emotional expression recognition, compared with patients with major depression and healthy control subjects. Methods: We studied performance in facial expression recognition and facial sex recognition paradigms, using original morphed faces, in a population with schizophrenia ( n = 29) and compared their scores with those of depression patients ( n = 20) and control subjects ( n = 20). Results: Schizophrenia patients achieved lower scores than both other groups in the expression recognition task, particularly in fear and disgust recognition. Sex recognition was unimpaired. Conclusion: Facial expression recognition is impaired in schizophrenia, whereas sex recognition is preserved, which highly suggests an abnormal processing of changeable facial features in this disease. A dysfunction of the top-down retrograde modulation coming from limbic and paralimbic structures on visual areas is hypothesized.


Author(s):  
A M A Hammouda ◽  
G E Mady

The measurement of carbamylated haemoglobin is a useful indicator of uraemic state during the preceding few weeks in patients with renal failure. In diabetic uraemic patients with hyperglycaemia, glycation of haemoglobin may interfere with its carbamylation, as both reactions involve the free amino groups of the protein. The aim of this study was to investigate the carbamylation of haemoglobin in the presence of hyperglycaemia. The study included 29 patients with chronic renal failure on regular haemodialysis, 14 diabetic and 15 non-diabetic patients, and 10 healthy controls. We found a significant correlation between the degree of haemoglobin carbamylation and mean blood urea concentration in both uraemic and control subjects. Carbamylation of haemoglobin was higher in both diabetic and non-diabetic chronic renal failure patients, but there were no significant differences between the groups regarding mean blood urea concentration or level of haemoglobin carbamylation. Carbamylated haemoglobin per unit of blood urea concentration was lower in the diabetic patients. Using a correction formula to account for the degree of haemoglobin glycation, there was no longer a significant difference in carbamylation per unit of blood urea concentration. In vitro incubation of red blood cells from six healthy and six diabetic non-uraemic patients in 70mmol/L urea showed a significantly lower carbamylation in the diabetic patients, but there was no significant difference when using corrected carbamylated haemoglobin values. We conclude that glycation of haemoglobin affects its carbamylation and that monitoring of uraemia in a diabetic patient necessitates the use of carbamylated haemoglobin value corrected for the degree of glycation.


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