Neurocognitive impairment in type 2 diabetes mellitus.

There is emerging evidence that cognitive impairment could be a diabetes mellitus-related complication. It has been suggested that diabetic people are at increased risk of cognitive decline, since the metabolic and vascular disturbances of the disease affect brain function. Additionally, prolonged exposure to olther potential detrimental factors leads to irreversible cognitive decrements over time due to the aging process. Neurocognitive impairment signifies decreased performance in cognitive domains such as verbal and nonverbal memory, both immediate and delayed memory, executive function, attention, visuospatial and psychomotor performance, information processing speed, semantic knowledge, and language abilities. The aim of the present article is to review the existing literature on the issue of the neurocognitive decline in type 2 diabetes. A literature search of databases was performed, using as keywords "diabetes" and "cognitive impairment," and the reference list of papers so identified were examined, with only English language papers being used. Understanding and preventing diabetes-associated cognitive deficits remains a key priority for future research. It is important to ascertain whether interventions to delay diabetes onset or better control of established disease could prevent some of its adverse effects on cognitive skills.

Association of brain natriuretic peptide and adrenomedullin plasma levels with left ventricular filling pressures in end-stage renal disease patients on hemodialysis.

OBJECTIVE: Adrenomedullin (ADM) and brain natriuretic peptide (BNP) are known to be associated with elevated left ventricular filling pressures. However, little is known about this association in hemodialysis (HD) patients with preserved left ventricular ejection fraction (LVEF). Our objective was to evaluate the potential association between E/e' ratio and plasma levels of BNP and ADM in end-stage renal disease (ESRD) patients with preserved LVEF undergoing chronic hemodialysis. PATIENTS AND METHODS: The study group enrolled 62 ESRD patients treated with hemodialysis three times weekly. BNP and ADM plasma concentration measurements and echocardiographic examination were performed 30 minutes after hemodialysis. E/e' ratio, evaluated by Tissue Doppler imaging and measured at the basal septum, was used as a surrogate marker for assessing left ventricular filling pressures. RESULTS: The mean age of patients was 62 ± 25 years. The mean BNP and ADM values after hemodialysis were 0.40 ± 6.73 ng/ml and 0.06 ± 2.12 ng/ml, respectively. Elderly patients with hypertrophied left ventricles and larger left atria displayed higher E/e' values. BNP (r = 0.324. p = 0.018) and ADM (r = 0.319, p = 0.042) plasma levels were positively and significantly associated with E/e΄. Multivariate regression analysis including BNP, ADM, age, hemodialysis duration, left ventricular end-systolic volume index, LVEF, left ventricular mass index and left atrium volume index, revealed that ADM (p-value 0.025) but not BNP levels, were independently associated with the E/e' ratio. CONCLUSIONS: ADM, but not BNP, was independently associated with septal E/e' in HD patients with preserved LVEF. ADM plasma levels can be used as a surrogate index to assess left ventricular filling pressures in HD patients.

Effect of neonatal spinal transection and dorsal rhizotomy on hindlimb muscles.

The purpose of this study was to elucidate the effect of deafferentation on spinal motoneurons. We studied the effects of spinal cord transection and/or dorsal rhizotomy upon the contractile properties of EDL and soleus muscle, as well as on the number of motoneurons corresponding to these muscles. Neonatal Wistar rats were randomly divided into four groups in which spinal midthoracic section (T8-T10), unilateral dorsal lumbar rhizotomy (L3-S2) or both procedures were performed on the second postnatal day (PND2). Another group served as unoperated control. At 2 months of age, the animals were evaluated for the contractile properties of a fast (EDL) and a slow (soleus) muscle. Isometric tension recordings were elicited by way of sciatic nerve branches stimulation. In addition, the incremental method was applied for the determination of the number of motor units supplying the two muscles, which was also verified by using the horseradish peroxidase (HRP) method of reverse labeling of motoneurons. Muscle alterations were confirmed by the usual biochemical staining. Our results, in agreement with the data from other researchers, show that significant muscle atrophy takes place after all experimental procedures. Additionally, spinal cord section alters the development of the dynamic properties of soleus muscle, which attains a fast profile. Following transection, the number of motor units remained unaltered, while rhizotomy affected only the soleus by reducing its motor units. The combined procedure affected both muscles, indicating that adequate synaptic input is essential for motoneuron survival.

Magnesium administration provokes motor unit survival, after sciatic nerve injury in neonatal rats.

BACKGROUND: We examined the time course of the functional alterations in two types of muscles following sciatic nerve crush in neonatal rats and the neuroprotective effect of Mg2+. METHODS: The nerve crush was performed on the 2nd postnatal day. MgSO4*7H2O was administered daily for two weeks. Animals were examined for the contractile properties and for the number of motor units of extensor digitorum longus and soleus muscles at three postnatal stages and adulthood. Four experimental groups were included in this study: i) controls, ii) axotomized rats, iii) magnesium treated controls and iv) axotomized and Mg2+-treated rats. RESULTS: Axotomy resulted in 20% MU survival in EDL and 50% in soleus. In contrast, magnesium treatment resulted in a significant motor unit survival (40% survival in EDL and 80% in soleus). The neuroprotective effects of Mg2+ were evident immediately after the Mg2+-treatment. Immature EDL and soleus muscles were slow and fatigueable. Soleus gradually became fatigue resistant, whereas, after axotomy, soleus remained fatigueable up to adulthood. EDL gradually became fastcontracting. Tetanic contraction in axotomized EDL was just 3,3% of the control side, compared to 15,2% in Mg2+-treated adult rats. The same parameter for axotomized soleus was 12% compared to 97% in Mg2+-treated adult rats. CONCLUSIONS: These results demonstrate that motoneuron death occurs mostly within two weeks of axotomy. Magnesium administration rescues motoneurons and increases the number of motor units surviving into adulthood. Fast and slow muscles respond differently to axotomy and to subsequent Mg2+ treatment in vivo.

Effect of ropivacaine infiltration on muscle regeneration: a morphometric analysis.

BACKGROUND/AIM: Local anaesthetic myotoxicity is a well described phenomenon resulting in reversible muscle damage. Considering that in previous studies microscopic images were evaluated without quantification of morphologic characteristics, the aim of the present study was evaluate muscle regeneration after local anaesthetic infiltration. MATERIALS AND METHODS: Wistar rats underwent injection of the left tibialis anterior muscle with ropivacaine (0.75%, group HC or 0.375%, group LC), while the contralateral muscle was injected with saline (group SL). Six weeks later, the muscles were dissected, stained using acid ATPase and examined under light microscope coupled with a computer imaging system for morphometric analysis. Sections were evaluated regarding the content of different muscle fibre types (type I, IIa and IIb), fibre cross-section area and perimeter. RESULTS: Groups were comparable regarding the ratio of different muscle fibre types. Regenerated type I fibres of both HC and LC groups had significant greater mean cross-sectional area and perimeter, compared to SL fibres. No signs of necrosis or inflammation were observed. Type IIa and IIb fibres didn't show significant differences. CONCLUSIONS: Regenerated muscles, following local anaesthetic application, showed long-term morphological differences, which could lead to impaired function. Further studies are needed, in order to clarify the underlying cellular mechanisms and the subsequent possible functional impairment.

Sciatic nerve crush evokes a biphasic TGF-beta and decorin modulation in the rat spinal cord.

BACKGROUND AND AIM: Inherent property of the motoneurons of the peripheral nervous system is their ability to recover, at least in part, upon injury. To this end different factors are expressed and are thought to play important role in the regeneration processes. These factors are diverse, and range from transcription factors and chemokines, to molecules of the extracellular matrix. Transforming growth factor beta (TGF-beta) is a protein with diverse actions controlling cell growth and proliferation. In the extracellular matrix it is found bound to decorin a proteoglycan involved in cell adhesion and cell signaling. In the present study we investigate the expression of TGF-beta and decorin at different time points, in the regenerating sciatic nerve of a seven day old rat, having suffered nerve crush injury, over a period of one month. MATERIALS AND METHODS: To achieve this, we evoked injury to male Wistar rats by exposing and applying pressure to the sciatic nerve using watchmaker's forceps. After that at 12 h, 24 h, 48 h, 72 h, one week, and one month intervals we investigated the gene expression of decorin using RT-PCR, and followed the expression of TGF-beta molecule by immunohistochemistry in frozen sections of the L4-L5 region of the rat spinal cord. RESULTS: We report that both decorin mRNA and TGF- protein exhibit a concerted, biphasic expression after 12 hours and one month having the animal suffered the nerve crush. DISCUSSION: Our data reveal a biphasic modulation of TGF-beta protein and decorin mRNA expression at lumbar segment of the spinal cord of animals having suffered unilateral sciatic nerve crush. We postulate that their concerted expression both at an early and a late phase after the nerve injury is of importance and can be part of a repair or neuroprotective mechanism as yet unclarified.

Ropivacaine myotoxicity after single intramuscular injection in rats.

BACKGROUND AND OBJECTIVE: We conducted this study in order to evaluate the potential myotoxic effects of ropivacaine after single injection in rats and the time-course of the possible damage. METHODS: One hundred and twenty-eight male Wistar rats were allocated to four different groups. The first three groups received intramuscular injections with ropivacaine 0.75%, ropivacaine 0.5% and normal saline, respectively, into the right tibialis anterior muscle. The fourth group received needle puncture without injection. Eight rats from each group were sacrificed 2, 4, 7 and 30 days after injection. Samples were blindly examined under light microscope for evidence of myotoxicity, scored as 0 = no damage to 3 = myonecrosis and statistically analysed. Samples obtained 7 days after injection were also examined under transmission electron microscope. RESULTS: Ropivacaine 0.75% and ropivacaine 0.5% caused extensive destruction to muscles fibres, compared to saline or needle on days 2, 4 and 7. Statistically significant differences were found in muscle damage by drug injections among all groups except for saline vs. needle groups. Thirty days after injections all sample appearances had returned to normal. CONCLUSIONS: Ropivacaine after single intramuscular injection caused reversible muscle damage in a dose-dependent manner.