The effect of FAAH, MAGL, and Dual FAAH/MAGL inhibition on inflammatory and colorectal distension-induced visceral pain models in Rodents.

BACKGROUND: Recent studies showed that the pharmacological inhibition of endocannabinoid degrading enzymes such as fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) elicit promising analgesic effects in a variety of nociceptive models without serious side effects. However, the full spectrum of activities is not observed upon inhibition of either FAAH or MAGL enzymes alone and thus dual FAAH and MAGL inhibitors have been described. Visceral pain is strongly associated with inflammation and distension of the gut. Thus, we explored the comparable effects of FAAH, MAGL, and dual FAAH/MAGL inhibitors on inflammatory and mechanically evoked visceral pain models. METHODS: Visceral inflammatory and distension-induced pain were assessed with the 0.6% acetic acid writhing test in mice and colorectal distension (CRD) test in rats, respectively. The selective FAAH inhibitor PF 3845, MAGL inhibitor JZL 184, dual inhibitor JZL 195, and the cannabis analog CP 55,940 were given systemically 30 min prior to nociceptive testing. KEY RESULTS: PF 3845 (5, 10, and 20 mg/kg), JZL 184 (5, 10, and 20 mg/kg), and JZL 195 (5, 10, and 20 mg/kg) elicit dose-dependent antinociceptive in the acetic acid writhing test. In the CRD model, while JZL 195 (5, 10, or 20 mg/kg) and PF3845 (10, 20, and 40 mg/kg) produced dose-dependent antinociceptive effects comparable to those of CP 55,940 (0.1, 0.3, or 1 mg/kg), JZL 184 (10, 20, and 40 mg/kg) alone did not alter the visceromotor response (VMR). CONCLUSIONS & INFERENCES: The selective FAAH inhibitor and dual FAAH/MAGL inhibitors were effective in both inflammatory and mechanically evoked visceral pain, while the MAGL inhibitor elicited an analgesic effect in inflammatory, but not in distension-induced, visceral pain.

Cutaneous silent period changes in Type 2 diabetes mellitus patients with small fiber neuropathy.

OBJECTIVE: Small myelinated (A-delta) and unmyelinated (C) somatic sensory fibers are initially affected and may be the earliest exhibited sign of neuropathy in glucose dysmetabolism. Cutaneous silent period (CSP) is an inhibitory spinal reflex and its afferents consist of A-delta nerve fibers. The aim of this study was to evaluate CSP changes in Type 2 diabetic patients with small fiber neuropathy. METHODS: Forty-three patients and 41 healthy volunteers were included. CSP latency and duration, as well as CSP latency difference of the upper and lower extremities, were examined. RESULTS: Nerve conduction studies were within normal limits in both groups. Lower extremity CSP latency was longer (122.1+/-15.5 vs. 96.4+/-6.4 ms; p<0.001), CSP duration was shorter (29.5+/-8.9 vs. 43.1+/-5.0 ms; p<0.001), and latency difference was longer (48.1+/-12.6 vs. 22.7+/-3.7; p<0.001) in patients than controls. The difference was more significant in patients with neuropathic pain. No significant difference existed in upper extremity on CSP evaluation. CONCLUSION: The CSP evaluation together with nerve conduction study, has been demonstrated to be beneficial and performance of latency difference in addition to CSP latency and duration may be a valuable parameter in electrophysiological assessment of diabetic patients with small fiber neuropathy. SIGNIFICANCE: An additional CSP evaluation may be considered in cases which nerve conduction studies do not provide sufficient information.

Sunrise-related headache: case report.

A male, 34 years of age, suffers from headaches, red and watery eyes. The headaches began in childhood; the frequency of headaches has increased over the years and in the last decade headaches have occurred on a daily basis. If he wakes up before sunrise he feels much better and free of a headache; however, once he continues to sleep during and after sunrise, he suffers from tiredness, headache and nervousness. On magnetic resonance imaging (MRI), benign neuroepithelial cysts or a chronic infarct area was reported at the junction of the left medio-lateral zone of hypothalamus. After repeated MRI examinations, it was decided that the lesion on the left medio-lateral zone of hypothalamus may have disrupted the pineal gland and changed melatonin secretion. It was decided to treat him with 3 mg melatonin daily before going to bed. After a week of treatment, the patient reported that he felt very fresh and was virtually free of headaches.

Early diagnosis and treatment reverse clinical features in Hoffmann's syndrome due to hypothyroid myophaty: a case report.

Hypothyroidism is a frequently diagnosed endocrine disorder that has characteristic clinical signs and symptoms. Myopathy is one of the manifestations of hypothyroidism and relatively common. We report a case of Hoffmann's Syndrome due to hypothyroid myopathy documented by clinical features, laboratory findings and positive response to thyroid hormone replacement therapy. A man, age of 22, was diagnosed as having primary hypothyroidism at the age of five, had been describing progressive weakness in his arms and legs for two months and complained about generalized muscle cramps and pain. He was diagnosed with Hoffmann's syndrome with low levels of thyroid hormones and high levels of muscle enzymes. After six months of thyroid hormone replacement therapy, both the clinical picture and laboratory findings were remarkably improved.

Effect of methylphenidate on auditory event related potential in boys with attention deficit hyperactivity disorder.

OBJECTIVE: Event related brain potentials (ERPs) is a non-invasive technique giving knowledge about neural activity associated with sensory and cognitive information processing. The aims of the present study were to investigate amplitude and latency of P100, N200, and P300 in parietal and frontal areas in children with attention deficit hyperactivity disorder (ADHD), and in healthy children, and to determine the effect of methylphenidate (MPH) on these ERPs indices in ADHD group. METHODS: ERP indices, latencies of parietal P3 (PP3L), P1 (PP1L), N2 (PN2L), and frontal P1 (FP1L), N2 (FN2L), P3 (FP3L), and amplitudes of parietal P3 (PP3A), P1 (PP1A), N2 (PN2A), and frontal P1 (FP1A), N2 (FN2A), and P3 (FP3A), using an auditory oddball paradigm were recorded before and under MPH treatment in boys with ADHD, and in 23 healthy children. RESULTS: Before MPH treatment, PP3L was significantly longer and PP3A, PN2A, FN2A, and FP3A smaller in children with ADHD compared to healthy children (all P values < .05). No significant difference was found in PP1L, PP1A, PN2L, FP1L, FP1A, FN2L, and FP3L between ADHD and control group (all P values > .05). MPH treatment resulted in a significant decrease in PP3L, PN2L, and FP3L, and increase in PP3A, PP1A, and FP3A (all P values < .05). There was no significant difference in PP1L, PN2A, FP1L, FP1A, FN2L, and FN2A between before MPH and under MPH treatment in ADHD subjects (all P values > .05). Under MPH treatment, PP3L, PP3A, PP1L, PP1A, PN2L, FP1L, FP1A, FN2L, FP3L, and FP3A were not significantly different between children with ADHD and healthy controls (all P values > .05). However, PN2A and FN2A were significantly smaller in ADHD subjects compared to controls (both P values < .05). CONCLUSION: This study provides indirect evidence that ADHD subjects are associated with abnormalities in signal detection (inattention) and discrimination, and information processing. In addition, present study has shown that except FN2A and PN2A, MPH normalizes ERP indices, which suggested that MPH may be effective on impaired information processing in ADHD, but not on the receiving information.

Nutritional effects on auditory brainstem maturation in healthy term infants.

OBJECTIVE: To assess the effects of dietary long chain polyunsaturated fatty acid (LCPUFA) supplementation on auditory brainstem maturation of healthy term newborns during the first 16 weeks of life by measuring brainstem auditory evoked potentials (BAEPs). DESIGN: Throughout the 16 week study period, infants in the formula A group (n = 28) were assigned to be fed exclusively with the same formula supplemented with DHA, and infants in the formula B group (n = 26) were assigned to receive only a DHA unsupplemented but otherwise similar formula. During the study period, the first 26 consecutive infants to be fed exclusively on their mother's milk for at least the first 16 weeks of life were chosen as the control group. BAEP measurements were performed twice: at the first and 16th week of age. RESULTS: There were no significant differences among the study and control groups in the BAEP measurements performed at the study entry. At 16 weeks of age, all absolute wave and interpeak latencies in the study and control groups had significantly decreased. The decreases were significantly greater in the formula A and control groups than in the formula B group. CONCLUSIONS: Infants fed on human milk or a formula supplemented with LCPUFAs during the first 16 weeks of life show more rapid BAEP maturation than infants fed on a standard formula. Although the clinical importance and long term effects of these findings remain to be determined, routine supplementation of formulas with LCPUFAs should be considered.

Effect of mannitol in experimental spinal cord injury: an ultrastructural and electrophysiological study.

BACKGROUND: Although many experimental and clinical studies were performed on the pathophysiology and treatment of spinal cord injury (SCI), the electrophysiological and ultrastructural changes of the spinal cord were not precisely evaluated. AIMS: To investigate the effect of mannitol on Somatosensory Evoked Potentials (SSEP), postoperative neurological recovery and ultrastructural findings after an experimental SCI. SETTING: The experimental microsurgery laboratory of a university hospital. DESIGN: A prospective, randomized animal study. MATERIAL AND METHODS: Sprague-Dawley rats were used and divided into three groups (Groups I-III) for this study. Those in Group I were control animals who underwent laminectomy only, and non-traumatized spinal cord samples were obtained 2 weeks later. SCI was produced in Groups II and III using clip compression technique, and cord samples were obtained 2 weeks later. The rats in Group II received 2 g/kg of 20% mannitol intraperitoneally, immediately and three hours after trauma was induced; and those in Group III received the same amount of 0,9% NaCl in the same manner. Preoperative and postoperative SSEP records at the end of 2 weeks were obtained. Electron microscopy examination of the cord samples was done at 2 weeks postoperatively. STATISTICAL ANALYSIS USED: Fischer's Exact Test. RESULTS: SSEP records, ultrastructural findings and clinical recovery showed that minor neural damage and significant recovery occurred in Group II. CONCLUSION: This study demonstrates that the administration of 2 g/kg of 20% mannitol produces significant improvement in the neural structures and protects the spinal cord following injury.

Comparison of sensitivities of macro EMG and concentric needle EMG in L4 radiculopathy.

The purpose of this study was to compare the sensitivities of macro EMG (mEMG) and concentric needle EMG (cnEMG) in showing abnormality in L4 radiculopathy. We evaluated 23 patients with clinically and radiologically proven L4 root lesions. Among these patients, 21 (92%) had cnEMG abnormalities. Out of 21 patients with cnEMG abnormality, 3 (14%) had fibrillations and positive sharp waves, 8 (38%) had interference pattern abnormality and all of them had motor unit potential (MUP) abnormality on quantitative MUP analysis. Seventeen patients (74%) had mEMG abnormality. Diagnostic yield of cnEMG is higher than mEMG in L4 radiculopathy. mEMG may not contribute much to the diagnosis of lumbar radiculopathy.

Median nerve somatosensory evoked potentials recorded with cephalic and noncephalic references in central and peripheral nervous system lesions.

Somatosensory evoked potentials (SSEP) to electrical stimulation of the median nerve by using cephalic and noncephalic references were studied to detect the generator sources of short latency evoked potentials in 29 patients with cerebral, brainstem, spinal and peripheral nerve lesions. Patients were divided into six groups according to the localization of their lesions: group 1: cortical and subcortical lesions, group 2: basal ganglion lesions, group 3: pons and mesencephalon lesions, group 4: diffuse cerebral lesions, group 5: cervical cord lesions, group 6: brachial plexus lesions. Potentials were recorded using cephalic and noncephalic references after median nerve stimulation. Evidence obtained from patients suggested the following origins for these short latency SSEPs: P9 may arise in brachial plexus, P11 in dorsal basal ganglions or dorsal column, P13 and P14 in the nucleus cuneatus and lemniscal pathways, N16 in subthalamic structures and most likely mid and lower pons, N18 from the thalamus and thalamocortical tract, and N20 from primary somatosensory cortex.

Malondialdehyde, glutathione peroxidase and superoxide dismutase in peripheral blood erythrocytes of patients with acute cerebral ischemia.

The levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD-1) were measured in the red blood cells (RBC) of 34 patients with acute ischemic hemispheric stroke on the first and seventh day after their stroke onset, and compared with 30 control individuals matched for sex, age and stroke risk factors. Within the first 24 h after stroke, SOD and GSH-Px activities were significantly decreased and MDA levels were significantly elevated in the patients compared with control subjects. Decrease in SOD and GSH-Px activities and increase in MDA levels showed significant correlation with infarct size, initial stroke severity assessed by NIH stroke scale and poor short-term prognosis. Observed changes in the RBC oxygen scavenging process returned to values not different from those of control subjects within seven days after stroke. Our results indicated that antioxidant enzyme concentrations decreased below normal levels in the acute period following ischemic stroke. Until the recovery of antioxidant defence mechanisms, which occurred up to seven days after stroke onset according to our results, the use of neuroprotective therapy against oxyradical injury seems reliable.

Median nerve somatosensory evoked potentials: recording with cephalic and noncephalic references.

We performed both cephalic and noncephalic reference SEP recordings with median nerve stimulation in normals and compared the results obtained from both recordings. Median nerve SEP with non cephalic reference revealed four positive and three negative potentials on scalp, while median nerve SEP with cephalic reference showed only one negative potential on scalp. We conclude that potentials originated from subcortical regions can be recorded from scalp by using noncephalic reference, which is not possible by cephalic reference and potential N20 obtained from somatosensory cortex by using cephalic reference does not present a single potential, consisting of combination of a few potentials. To differentiate these potentials, noncephalic reference must be used.