Objective To clarify the clinical features,therapeutic strategy and prognosis of lipid storage myopathy (LSM).Methods The clinical data and therapeutic effects of 42 LSM patients were summarized retrospectively.All patients were followed up to evaluate their prognosis.Results Data of short-term therapeutic results of all the 42 patients were available.Thirty-three cases were placed in low- doses prednisone and 9 cases in riboflavin.All patients showed marked and quick improvement of symptoms within one month.Among thirty-two patients followed up for more than one year,26 cases had a full recovery and 6 remained to have intolerance to heavy exercise.Thirteen patients had relapses of muscle weakness in various degrees and most of which were induced by exertion,exposure to coldness and upper respiratory tract infection.In 5 patients the symptoms were recurred for more than one time.Among 13 cases with relapses, 7 had family history.Conclusions Our data suggest that LSM is a treatable disease and well responsive to low-doses prednisone.The disease tends to recur,especially in patients with family history.Glutaric aciduria type Ⅱ should be considered in LSM patients who are responsive well to riboflavin,indicating drug therapeutic strategy for LSM should be based on the etiology of the disease.

Objective To investigate the clinical,neuroimaging and myopathological features of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes(MELAS).Methods The clinical manifestations,neuroimaging and myopathological features of 31 patients with MELAS diagnosed in our Neuromuscular Center in the recent 7 years were retrospectively analyzed.A3243G point mutations were analyzed by RFLP method in 10 patients.Results ①Clinical features:There were 18 male patients and 13 female patients.The age of onset ranged from 3 to 43 years,averaging 21.9 years.The averaged duration was 4.9 years.Thirteen patients in this group had family history of maternal inheritance pattern.The main clinical manifestations included short stature(26 patients),recurrent headache and vomiting(24 patients), muscle weakness(22 patients),epileptic seizure(21 patients),cognitive decline(19 patients),visual disturbance(17 patients),sensorineural deafness(16 patients),ataxia(6 patients),psychiatric symptom (8 patients),external ophathalmoplegia(2 patients)and diabetes mellitus(9 patients).The serum CK level was slightly elevated in 6 patients,and the fasting blood lactic acid was increased in 15 of the 18 detected patients.②Neuroimaging features:The stroke-like lesions were mostly confined to cerebral cortex, including temporal lobe(24 patients),occipital lobe(21 patients),parietal lobe(12 patients)and frontal lobe(4 patients).Three patients had deep white matter involvement.Migrating stroke-like lesions were confirmed in 4 patients by repeated cranial CT/MRI examination.In addition,cerebral atrophy(17 patients)and bilateral basilar ganglion calcification(11 patients)were found.③Myopathological features: Scattered ragged red fibers(RRF)in various number were found in all the patients by MGT staining.Other founding included strongly SDH-reactive blood vessel(27 patients),COX enzyme deficiency(19 patients), and mild to moderate lipid storage in RRF(20 patients).④MtDNA analysis showed 9 patients with A3243G point mutation in all the detected 13 patients.Conclusion The clinical and neuroimaging features may offer important clue to the diagnosis of MELAS,but a definite diagnosis of MELAS relies on the myopathology and mtDNA mutation analysis.

In this study, reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the changes in mRNAs levels of preproadrenomedullin (ppADM) gene encoding adrenomedullin (ADM) and the essential receptor components of ADM, calcitonin receptor-like receptor (CRLR), and the receptor activity modifying protein 2 and 3 (RAMP2 and RAMP3) in the medulla oblongata, hypothalamus, midbrain, pituitary gland and adrenal gland of the stress-induced hypertensive rats. It was shown that chronic foot-shock and noise stress for 15 consecutive days induced a significant increase in systolic blood pressure (SBP) and unique changes in ppADM and its receptor components mRNAs in all areas studied. As compared with the control group, the level of ppADM mRNA, normalized against a glyceraldehydes-3-phosphate dehydrogenase (GAPDH) control, was up-regulated in the hypothalamus-pituitary-adrenal (HPA) axis, but down-regulated in the medulla oblongata and midbrain (P<0.01 and P<0.05, respectively). The relative amount of CRLR mRNA was higher in the hypothalamus than that in other areas. The level of CRLR mRNA expression was significantly increased in the medulla oblongata of the stress group (P<0.01), but decreased in the midbrain (P<0.01) as well as hypothalamus(P<0.05), as compared with that of the control group. Chronic stress for 15 consecutive days produced an increase in the level of RAMP2 mRNA expression in the medulla oblongata (P<0.01) and a decrease in the adrenal gland (P<0.01), as compared with the control. No significant stress-related changes in RAMP2 mRNA were observed in the midbrain, hypothalamus and pituitary gland. The amount of RAMP3 mRNA was relatively higher in the midbrain and hypothalamus than that in the medulla oblongata, adrenal gland and adrenal gland. Stress-induced hypertensive rats exhibited an increased RAMP3 mRNA expression in the hypothalamus and pituitary gland (P<0.01 and P<0.05, respectively) and a decrease in the adrenal gland and midbrain (P<0.05). No significant stress-related change in RAMP3 mRAN was observed in the medulla oblongata. Taken together, our results indicate that the significant changes in ppADM and its receptor components mRNAs expression in the HPA axis and autonomic centers may be related to the development of the stress-induced hypertension. Nevertheless, the pathophysiological significance of brain-derived ADM and its receptors in stress and blood pressure regulation and their roles in stress-induced hypertension still await further investigation.
Adrenomedullin ; Animals ; Brain Stem ; metabolism ; Hypertension ; etiology ; metabolism ; Hypothalamo-Hypophyseal System ; metabolism ; Male ; Peptides ; genetics ; metabolism ; Pituitary-Adrenal System ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenomedullin ; Receptors, Peptide ; biosynthesis ; genetics ; Stress, Physiological

To investigate the eletrophysiological effect of rat adrenomedullin (rADM) on barosensitive neurons in the rostral ventrolateral medulla (rVLM) and its potential mechanisms, the extracellular recording and multi-barrel iontophoresis methods were used. Of the 29 barosensitive neurons in the rVLM, 20 neurons demonstrated excitatory response to iontophoretically applied rADM and increased the firing rate from (10.8 +/- 2.7) spikes/s to (14.6 +/- 3.6), (19.8 +/- 4.7) and (31.9 +/- 6.4) spikes/s (P<0.05, n=20) at the current of 30, 60 and 90 nA, respectively. Application of human adrenomedullin (22-52) [hADM (22-52)], a specific antagonist of rADM receptor, distinctly attenuated the augmentation of firing rate induced by rADMjthe firing rate was increased by 15.4% [(11.4 +/- 2.5) spikes/s, P<0.05, n=10]. Another antagonist, human calcitonin gene-related peptide (8-37) [hCGRP (8-37)] had no significant effect on rADM-induced excitation. Other 23 barosensitive neurons were recorded to test the influence of nitric oxide synthase (NOS) inhibitors on the excitatory effect of rADM. In 10 neurons, 7-NiNa (neuronal NOS inhibitor) decreased the firing rate from (10.1 +/- 3.5) spikes/s to (7.5 +/- 2.5), (5.3 +/- 2.1) and (3.1 +/- 1.4) spikes/s (P<0.05, n=10) at the current of 10, 20 and 40 nA, respectively. The excitatory effect of rADM (60 nA, 30 s) during 7-NiNa application was nearly eliminated and the magnitude of firing rate was increased only by 17% of the basal level (6.2 +/- 1.9) spikes/s (P<0.05, n=7). While aminoguanidine (AG, iNOS inhibitor) increased the firing rate at the resting level from (11.5 +/- 5.1) spikes/s to (17.8 +/- 5.6), (22.5 +/- 6.3) and (29.1 +/- 6.4) spikes/s (P<0.05, n=8) at the current of 10, 20 and 40 nA in 8 barosensitive neurons, respectively. When rADM (60 nA, 30 s) was delivered during AG iontophoresis period, the firing rate significantly increased by 60% of the basal level [(22.5 +/- 6.3) spikes/s, n=5]. These results indicate that rADM activates the barosensitive neurons in the rVLM directly and acts as a cardiovascular regulator, and that this function might be mediated by its specific receptor. NO, mainly neuronal NOS-originated might be involved in the excitatory effect of rADM in the rVLM.
Adrenomedullin ; physiology ; Animals ; Electrophysiological Phenomena ; Male ; Medulla Oblongata ; physiology ; Neurons ; physiology ; Nitric Oxide ; physiology ; Nitric Oxide Synthase Type I ; physiology ; Pressoreceptors ; physiology ; Rats ; Rats, Sprague-Dawley

BACKGROUNDPolyunsaturated omega-3 fatty acids may beneficially influence healing processes and patient outcomes. The aim of this research was to study the clinical efficacy of fish oil enriched total parenteral nutrition in elderly patients after colorectal cancer surgery.

METHODSFifty-seven elderly patients with colorectal cancer were enrolled in this prospective, randomized, double-blind, controlled clinical trial. All patients received isocaloric and isonitrogenous total parenteral nutrition by continuous infusion (20 - 24 hours per day) for seven days after surgery. The control group (n = 28) received 1.2 g/kg soybean oil per day, whereas the treatment group (n = 29) received 0.2 g/kg fish oil and 1.0 g/kg soybean oil per day. Blood samples were taken pre-operatively, and at days one and eight after the operation. The plasma levels of CD4, CD8, CD4/CD8, interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were measured. Clinical outcomes were then analysed.

RESULTSPatient characteristics were comparable between the two groups. At day eight post-surgery, IL-6, TNF-α and CD8 titres were lower in the treatment group when compared to the control group; these results reached statistical significance. In the treatment group, there were fewer infectious complications and incidences of systemic inflammatory response syndrome (SIRS), and shorter lengths of hospital stay were observed. The total cost of medical care was comparable for the two groups. No serious adverse events occurred in either group.

CONCLUSIONSFish oil 0.2 g/kg per day administrated to elderly patients after colorectal surgery was safe and may shorten the length of hospital stay and improve clinical outcomes.

Aged ; CD4 Antigens ; blood ; CD4-CD8 Ratio ; CD8 Antigens ; blood ; Colorectal Neoplasms ; blood ; surgery ; Colorectal Surgery ; Female ; Fish Oils ; therapeutic use ; Humans ; Interleukin-6 ; blood ; Male ; Middle Aged ; Parenteral Nutrition, Total ; methods ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo analyze the clinical and pathological features of the centronuclear myopathy (CNM) in 5 Chinese patients and evaluate their diagnostic and differential diagnostic value.

METHODSA standard series of histochemical and enzymohistochemical investigations were performed on all muscle specimens of CNM cases obtained via biopsy. The clinical manifestations and myopathological features of 5 CNM patients were retrospectively analyzed.

RESULTSThe age of onset ranged from 3 to 12 years. All patients primarily presented with limb girdle muscle weakness. In 3 patients extraocular muscles, facial muscles and cervical muscles were affected, respectively. The proximal muscles were affected more seriously than the distal and the lower limbs more seriously than the upper. Tendon reflex was reduced and no evident muscular atrophy was seen. The course of the disease ranged from 4 to 46 years and progressed slowly. The ability of walking could be maintained for many years and the fast movements such as running and jumping were impaired early. The serum creatine kinase (CK) level was normal or elevated slightly. Electromyography showed myopathic pattern in all cases. Two patients (mother and son) were from the same family and the son's two siblings had similar symptoms indicating autosomal dominant inherited pattern. There was mild variation in fiber size and most small fibers were round. Interstitial tissue increase slightly. Fibers with centrally placed nuclei accounted for 23% - 93%. Neither necrotic and regenerated fibers nor infiltration of inflammatory cells were seen. Type I fiber predominance and hypotrophy were present in all patients. Abnormal arrangement of the sarcoplasmic strands in appearance of "spokes of a wheel", increased oxidative enzyme activity around centronuclear and perinuclear halo were observed in 2 patients by NADH-TR staining.

CONCLUSIONSFor the patients who had the onset during the childhood and presented with slow progressive limb girdle muscle weakness, disability of fast movements and normal serum CK level, the possibility of benign congenital myopathy should be considered. High percentage of centronuclear fibers as well as type I fiber predominance and hypotrophy in muscle biopsy pathology may provide a morphological evidence for the definite diagnosis of CNM.

Adolescent ; Adult ; Biopsy ; Child ; Child, Preschool ; Creatine Kinase ; blood ; Female ; Humans ; Male ; Middle Aged ; Myopathies, Structural, Congenital ; diagnosis ; pathology ; Retrospective Studies

Experiments were performed on male Sprague-Dawley (SD) rats anesthetized with a mixture of urethane and chloralose. A rat model of acute myocardial ischemia (AMI) was made by ligation of the left anterior descending branch of the coronary artery (LAD). After the LAD ligation, the ischemia area of the left ventricular wall became somewhat pale immediately. Under a light microscope, the pathological examination revealed that all the cells were swollen and in red color when the cardiac section was stained with hematoxylin basic fuchsin picric acid (HBFP), which indicated a typical change in the myocardial ischemia. In the AMI model, it was found that cardiac functions were markedly attenuated, such as decreases in the heart rate (HR), mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), maximal rate for left ventricular pressure rising and declining (+/-dp/dt(max)), velocity of contractile element (V(CE)) and total area of cardiac force loop (L(0)), and an increase in the left ventricular end diastolic pressure (LVEDP). In such AMI rats, application of electroacupuncture (EA) at "Neiguan" acupoints (Pe 6) for 20 min could obviously improve the above-mentioned cardiac functions. After microinjection of nitro-L-arginine (L-NNA), an inhibitor of nitric oxide synthase (NOS), was made into the rostral ventrolateral medulla (RVLM), the curative effect of EA on myocardial ischemia was reduced significantly or abolished, while after microinjection of normal saline of the same volume was made into the RVLM, the improving effect of EA remained. These results suggest that the effect of EA on myocardial ischemia is possibly mediated by the nitric oxide (NO) in the RVLM.
Acupuncture Points ; Animals ; Electroacupuncture ; Male ; Medulla Oblongata ; metabolism ; Myocardial Ischemia ; metabolism ; physiopathology ; Nitric Oxide ; physiology ; Rats ; Rats, Sprague-Dawley ; Ventricular Function

In this study, we used techniques of in situ hybridization, immunohistochemistry, electric stimulation of the dorsal periaquaductal gray of the midbrain (dPAG) and microinjection to investigate the changes of preproadrenomedullin (ppADM) gene expression encoding adrenomedullin (ADM) and ADM-like immunoreactivity (ADM-IR) in the medulla oblongata, especially in the rostral ventrolateral medulla (rVLM) of the rats receiving foot-shock and noise stress for 5 d, and the potential role of ADM in cardiovascular component of defense response in the rVLM. The results showed that ppADM mRNA and ADM-IR were widely distributed throughout the medulla oblongata. Highly labeled neurons were found in the ventrolateral reticular nucleus and hypoglossal nucleus. Moderately labeled neurons were seen in the facial, ambiguus, lateral reticular, paragigantocellular reticular, and inferior olivary nuclei. Weak signal was present over neurons of nucleus of the solitary tract. The expression of ppADM mRNA and ADM-IR increased significantly after foot shock and noise stress for 5 d as compared with that in control group (P<0.01). On the other hand, stimulation of the right dPAG raised the artery pressure (AP) rapidly from (116.4+/-8.9) mmHg to (140.0+/-9.8) mmHg, and heart rate (HR) from (378.0+/-7.5) beats/min to (413.0+/-8.2) beats/min, respectively, in the normotensive rats. After unilaterally microinjection of hADM(22-52) (a specific antagonist of ADM receptor, 1 pmol) into the right rVLM of the normotensive rats for 10 min, the rats received the stimulation of the dPAG again. Then we found that the DeltaAP and DeltaHR were lowered significantly within 60 min compared with those without hADM(22-52) application (P<0.05). After unilaterally microinjection of 0.1 pmol rat ADM (rADM) into the rVLM, dPAG stimulation caused no significant changes in DeltaAP and DeltaHR. Our results that foot-shock and noise stress induced significant increases of ppADM mRNA and ADM-IR in the rVLM, and microinjection of ADM receptor antagonist hADM(22-52) into the rVLM partly blocked the cardiovascular component of stress-defensive response induced by stimulation of the dPAG, suggest that ADM in the rVLM might be an important neurotransmitter or neuroregulator in the regulation of cardiovascular function in the stress-related defensive response.
Adrenomedullin ; physiology ; Animals ; Blood Pressure ; Electric Stimulation ; Heart Rate ; Medulla Oblongata ; physiology ; Microinjections ; Neurons ; physiology ; Periaqueductal Gray ; physiology ; Protein Precursors ; physiology ; Rats ; Rats, Sprague-Dawley

Increasing lines of evidence has been accumulated that nitric oxide (NO) and nitric oxide synthase (NOS) distribute plentifully in the rostral ventrolateral medulla (RVLM) and contribute to cardiovascular regulation. In the present study, the expressions of neuronal and inducible isoform of NOS (nNOS and iNOS) were observed in the RVLM of acute myocardial ischemia (AMI) Wistar rats experienced electroacupuncture (EA) treatment, thereby the cardiovascular effects of NO in the RVLM were investigated and the mechanism of acupuncture effect on AMI was inferred. The results indicated that in the AMI rats, cardiac functions were markedly attenuated with high serum level of brain natriuretic peptide (BNP) and norepinephine (NE), the number of nNOS-immunoreactive cells and nNOS mRNA exprossion in the RVLM area were increased, while those of iNOS were lowered. EA at "Neiguan" acupoints (Pe 6) 30 min daily for successive 5 d resulted in an improvement of the cardiac functions, decreases in NE and BNP levels; it also increased the expression of iNOS and decreased the expression of nNOS in the RVLM. These results suggest that the curative effect of acupuncture on AMI is possibly attributable to the differential regulation of NOS/NO in the RVLM, leading to decreased sympathetic outflow and improvement of cardiac functions.
Acupuncture Therapy ; Animals ; Electroacupuncture ; Medulla Oblongata ; metabolism ; Myocardial Ischemia ; metabolism ; therapy ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type I ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Rats ; Rats, Wistar

OBJECTIVETo study the difference of the gene expression profile and to identify the different expression after transfection of the ARL-1 gene.

METHODSThe cDNA probes were synthesized from total RNA of study group and control group, which was differentially hybridized to cDNA chips and confirmed by a gene specific semiquantitative reverse transcription polymerase chain reaction (RT-PCR).

RESULTSSix kinds of gene expression were increased and 9 kinds of gene expression were decreased. The findings were correlated with protein metabolism, signal pathway, metastasis, and drug resistance.

CONCLUSIONScDNA chips showed that gene expression profile of liver carcinoma cell was changed after transfection of the ARL-1 gene. It is a useful method in understanding the mechanism of drug resistance.

Aldehyde Reductase ; genetics ; Drug Resistance, Neoplasm ; Gene Expression Profiling ; Humans ; Liver Neoplasms ; drug therapy ; genetics ; Oligonucleotide Array Sequence Analysis ; Transfection