role of urinary cyclophilin A as a new marker for diabetic nephropathy

Background: Type 2 diabetes mellitus is the most common single cause of end-stage renal disease [ESRD], where diabetic nephropathy [DN] is considered the cause in almost half of all patients with ESRD. Despite the availability of many modern therapies for glycemic control, there are no specific curative treatments yet for DN and many diabetic patients still progressed to severe renal damage. Currently, albuminuria is the most commonly used marker to predict onset and progression of DN clinically. However, this traditional marker for DN lacks both sensitivity and specificity to detect early stage of DN. Furthermore, there is a lack of a strong association between albuminuria and glomerular filtration rate [GFR]. As such, it is crucial to find earlier and reliable markers for DN diagnosis and intervention providing an opportunity to stop the permanent damage caused by it

Objective: This study focuses on Cyclophilin A [CypA] in urine. CypA is a protein with ubiquitous characteristics, mostly distributed in the cytoplasm and facilitates protein folding and protein trafficking. It has relatively high expression level in normal kidneys. Recently, CypA has been reported to be a reliable novel marker for early diagnosis of DN

Subjects and Methods: Our study was conducted on 90 subjects of comparative age and sex. They were selected from Endocrinology Clinic after written consent at Ain Shams University Hospital and Railway Hospital. Participants were divided into: Group I: 30 healthy control subjects, Group II: 30 T2DM patients without albuminuria [normoalbuminuric], and Group III: 30 T2DM patients with albuminuric DN

Results: Our study showed that regarding the level of urinary CypA there was a highly statistical significant difference between the three groups [F= 221.730, p< 0.01], being higher in GII [normoalbuminuric] [1.69+/-0.87 ng/ml] than in GI [control] [0.55+/-0.14 ng/ml] [t= 7.04, p< 0.01] and higher in GIII [albuminuric DN] [6.01+/-1.61 ng/ml] than GII [t= 12.93, p< 0.001] and GI [t= 18.55, p< 0.0001]. In addition, we found that urinary CypA was significant higher in GIIIb [macroalbuminuria] [7.23+/-0.76 ng/ml] than in GIIIa [microalbuminuria] [4.79+/-1.25 ng/ml] [t= 6.49, p< 0.01]. It worth mentioning that, the level of urinary CypA started to increase significantly in stage 2 DN [2.49+/-0.50 ng/ml] in spite of normal level of albuminuria [no albuminuria] comparing with each of stage 1 DN [1.03+/-0.15 ng/ml], diabetics with no renal affection [0.99+/-0.45 ng/ml] and GI [healthy control] [0.55+/-0.14 ng/ml]. There was significant positive correlation between urinary CypA and each of: sCr in GII [r= +0.39, p< 0.05], GIIIa [r= +0.89, p< 0.001] and GIIIb [r= +0.99, p< 0.001] and ACR in GIIIa [r= +0.93, p< 0.001] and GIIIb [r= +0.98, p< 0.001]

Conclusion: Our study showed that there was a high significant difference in the level of urinary CypA between diabetic patients with any degree of renal affection and healthy subjects being higher in diabetics with renal affection even without the presence of albuminuria

Sleep disorders in peripheral neuropathy: a clinical and polysomnographic study

A fair number of sleep disorders are associated with peripheral neuropathies due to various mechanisms. Our aim was to assess different patterns of sleep disturbances in polyneuropathy patients. We studied the sleep architecture and sleep abnormalities in 20 polyneuropathy patients of different etiologies and 20 healthy control subjects. All patients and controls underwent clinical assessment and electromyographic and polysomnographic testing. Results revealed 40% of the patients reported positive sleep complaints mostly in the form of muscle cramps, numbness and tingling sensations in lower limbs and leg restlessness. The percentages of stages 1 and 2 were significantly increased and SWS was significantly reduced in patients compared to controls, the apnea /hypopnea index were increased specially in REM and 25% of the patients had a significant pathological periodic limb movement index [PLMI]. We concluded that sleep disordered breathing and periodic leg movements during sleep are not uncommon and important to recognize in patients with polyneuropathy and can cause frequent and increased awakenings

Assessment of the serum level of lnterlukin-12 and soluble vascular adhesion molecule-1 in multiple sclerosis patients

Multiple sclerosis [MS] is a complex and heterogeneous disease, and our understanding of the disease initiation mechanism and its wide clinical variability is limited. Cytokines and leukocyte endothelial adhesion play an important role in the initiation and maintenance of the inflammatory reaction in multiple sclerosis. The present study aimed to estimate the serum levels of IL-12 [a cytokine] and sVCAM-1 [an adhesion molecule] in different MS clinical subtypes and to assess their relationship to disease activity, grade of disability and MRI findings of cerebral atrophy. The study included 53 female patients suffering from definite MS [20 relapsing-remitting in remission [RRMS in remission], 16 relapsing-remitting in relapse [RRMS in relapse], and 17 secondary progressive [SPMS]] and 15 healthy age and sex matched controls. Patients were subjected to: thorough clinical evaluation, clinical grading of disability using Expanded Disability Status Scale [EDSS] and Magnetic resonance imaging [MRI] of the brain. For patients and controls, the serum levels of interleukin 12 [IL-12] and soluble vascular cell adhesion molecule-1 [sVCAM-1] were estimated. The mean serum levels of IL-12, and sVCAM-1 were significantly elevated in all MS groups compared to the control group. Significantly higher serum levels of IL-12, and sVCAM-1 were detected in SPMS versus RRMS groups [whether RRMS in relapse or in remission], and were significantly higher in RRMS in relapse versus RRMS in remission. The two biomarkers were significantly correlated to each other. Significant positive correlation was detected between mean EDSS score with mean serum levels of IL-12 and sVCAM-1. MRI signs of cerebral atrophy were detected in 17 patients, mainly from SPMS group. Patients with cerebral atrophy showed significantly higher serum levels of IL-12, and sVCAM-1 compared to patients without cerebral atrophy. Serum levels of IL-12 and sVCAM-1 are elevated in remission-relapse and progressive subtypes of MS and in MS associated with brain atrophy denoting that the inflammatory status in MS tends to persist in early and advanced stages of the disease. Immunomodulatory therapy targeting the above parameters might seem to be beneficial to delay disease progression and/or reduces lesion activity. Moreover, serum levels of IL-12, and sVCAM-1 were significantly correlated with the degree of disability induced by MS, thus suggesting their utility as reliable markers of disability in MS patients

Correlating brain stem auditory evoked potentials measurement to clinical and neurophysiological findings in patients with diabetes mellitus

Diabetes mellitus is a multisystem metabolic disorder. One of its rarely probed complications is brainstem dysfunction. We investigated brainstem auditory evoked potential studies [BAEPs] in diabetic patients, as well as its to microangiopathy. The study was conducted on 40 [type 1 and type 2] diabetic patients, calssified into: group [< 5 years duration of illness] and group 11 [> 5 years duration of illness]. The patients were examined clinically and neurologically. Neurophysiological tests in the form of: BAEPs, nerve conduction studies and flash electroretinography were performed to all patients. Urine analysis, instantaneous random blood sugar and funduscopy were also performed for patients. The BAEPs patients' results were compared to those of 30 normal subjects. Wave V absolute latency, III-V IPL and I-V IPL were positively correlated with the patients' age. Latency of wave III and V/I amplitude ratio were significantly higher in male patients. Tinnitus was associated with statistically significant increase in wave V latency, III-V IPL and I-V IPL. The same finding was reported in the 21 patients who showed evidence of nerve conduction abnormalities during nerve conduction studies. Retinal changes detected by fundus examination and abnormal F-ERG was associated with statistically significant increase in wave III latency. Brainstem dysfunction occurs early in the course of diabetes [type I and III similarly] and it is further affected by its duration. BAEP studies will be of help in detecting early subclinical central nervous system involvement in diabetic patients

Endothelin-1, brain natriuretic peptide and beta-atrial natriuretic peptide as new markers for left ventricular dysfunction

The aim of the present study was to assess plasma levels of neurohormones, ET-1, BNP and beta-ANP, in patients with acute MI, post-MI and dilated cardiomyopathy in order to clarify their value as markers for identifying left ventricular dysfunction in relation to the adopted echocardiographic assessment. ET-1, BNP, beta-ANP were measured by ELISA technique in 41 cardiac patients [23 patients had an ejection fraction [EF] of 0.45 and below, while 18 patients had an ejection fraction above 0.45 as proved by echocardiographic assessment]. Fifteen of them had acute MI [samples were taken after 38 hours from onset of chest pain] [group I], 16 patients were post-MI [samples were taken 1-2 months from onset of chest pain] [group II] and 10 patients had dilated cardiomyopathy [group III]. The results were compared to those of 10 healthy age-matched control subjects. In conclusion, this study confirmed the value of BNP and ET-1 as sensitive markers for identifying left ventricular dysfunction

Clincopathological significance of matrix metalloproteinases-9 [MMP-9] and its tissue inhibitor TIMP-1 in bronchopulmonary diseases

The matrix metalloprotienases [MMPs] are major proteolytic enzymes that are involved in extracellular matrix turnover. MMP-9 cleaves type IV collagen, which is an important constituent of basement membrane.These proteases play an important role in normal tissue homoestasis, but imbalance between MMPs and their tissue inhibitors [TIMPs] is thought to be a critical factor in regulating tissue remodelling. MMP-9 is mainly produced by inflammatory cells. The role of MMP-9 and TIMP-1 was investigated through the biochemical analysis of them in the bronchoalveloar lavage in different pulmonary diseases [74 patients]. As regards the comparison of MMP-9, TIMP-1, and their ratio levels of each patients group with other studied groups and controls, a highly significant statistical increase was observed in all studied groups than controls. The results of ANOVA study proved that TIMP-1 is the most discriminating parameter [F.ratio=37. 9], followed by MMP-9 [F ratio=22. 8] lastely the ratio [F. ratio=9. 3]. The ROC curves showed that TIMP-1 offers a superior diagnostic performance at a desicion level of 480 ng /ml compared to MMP-9 and the ratio in discrimination between cancer and non cancer patients. These findings suggest that both MMP-9 and its tissue inhibitor TIMP-1 play a central and specific roles in pulmonary structural remodlling. As well as, they are good diagnostic and prognostic markers in different bronchopulmonary diseases