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.

The present study was undertaken to investigate the linkage between angiotensin-(1-7) ［Ang-(1-7)］ and the release of amino acid neurotransmitters in the the rostral ventrolateral medulla (RVLM) by techniques of microinjection, microdialysis combined with high performance liquid chromatography (HPLC)-fluorescent detection. Unilateral microinjection of Ang-(1-7) into the RVLM of anesthetized rats produced an increase in mean arterial pressure (MAP) accompanied by an increased release of glutamate (Glu). In contrast, microinjection of Ang779, a selective antagonist of Ang-(1-7) receptor, caused a decrease in MAP with a decreased releaceof Glu and an increased release of glycine,taurine and r-aminobutyric acid.The pressor effect of Ang-(1-7)and the depressor effect of Ang779 were in part blocked by corresponding andtagonists of aminoacid receptors.These results suggest that the pressor effect of Ang-(1-7)in the RVLM may be partially due to an increased release of Glu,whereas the depressor effect of Ang779 may be partially attributed to a decreased release of Glu and an increased release of inhibitory amino acid neurotransmitters

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

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

OBJECTIVEImprovement in lung function was reported after acupuncture treatment of chronic obstructive pulmonary disease (COPD), but little is known about the underlying mechanisms. Because an immune response imbalance could be seen in COPD, we hypothesize that electroacupuncture (EA) may play a role in regulating inflammatory cytokines and contribute to lung protection in a rat model of smoke-induced COPD.

METHODSA COPD model using male Sprague-Dawley rats exposed to cigarette smoke was established. The rats were randomly divided into four groups (control, sham, COPD, and COPD plus EA), and COPD model was evaluated by measuring pulmonary pathological changes and lung function. EA was applied to the acupuncture point Zusanli (ST36) for 30 min/d for 14 d in sham and COPD rats. Bronchoalveolar lavage fluid (BALF) was used to measure levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and malonaldehyde (MDA).

RESULTSCompared with the control rats, COPD rats had significant changes in lung resistance (RL) and lung compliance (CL) (both P<0.01), bronchi and bronchiole airway obstruction (P<0.01), and levels of MDA, TNF-α, and IL-1β (P<0.01). There were no significant differences between the control and the sham groups. Compared with the COPD rats, the COPD plus EA rats had decreased RL and increased CL (both P<0.05), and reduced bronchi and bronchiole airway obstruction (P<0.05, P<0.01, respectively), while levels of TNF-α, IL-1β, and MDA in BALF were lowered (P<0.05 and P<0.01, respectively). However, TNF-α and IL-1β levels of the EA group rats remained higher than those of the control group (P<0.05).

CONCLUSIONEA at ST36 can reduce lung injury in a COPD rat model, and beneficial effects may be related to down-regulation of inflammatory cytokines. The anti-inflammatory and antioxidant effects may prolong the clinical benefit of EA.

Acupuncture Points ; Animals ; Bronchoalveolar Lavage Fluid ; immunology ; Disease Models, Animal ; Electroacupuncture ; Humans ; Interleukin-1beta ; immunology ; Male ; Pulmonary Disease, Chronic Obstructive ; etiology ; immunology ; therapy ; Rats ; Rats, Sprague-Dawley ; Smoking ; adverse effects ; Tumor Necrosis Factor-alpha ; immunology

BACKGROUNDThe down-regulation of constitutive nitric oxide synthase (cNOS) and up-regulation of inducible nitric oxide synthase (iNOS) are associated with the allergen-provocated airway hyperresponsiveness (AHR). This study aimed to determine whether their alteration also plays an important role in the AHR induced by lipopolysaccharide (LPS).

METHODSHartley male guinea pigs, weighing between 250 g and 350 g, were injected with LPS at a dose of 1 mg/kg every 24 hours for three days. A non-selective NOS inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), or a selective inducible NOS inhibitor, aminoguanidine (AG), were used thirty minutes before each injection of LPS. Airway reactions, nitric oxide (NO) production and inflammatory changes were detected 24 hours after the last dose of LPS.

RESULTSAG significantly decreased the NO production in the bronchoalveolar lavage fluid (BALF) and sharply reduced the intensity of bronchoconstriction to histamine challenge. L-NAME also significantly decreased the NO production in the BALF, but had no effect on airway reactions or, perhaps, a tendency to enhance the intensity of AHR.

CONCLUSIONSThe data suggest that inducible NOS contributes to the AHR induced by repetitive intraperitoneal LPS, and constitutive NOS was also involved.

Airway Resistance ; drug effects ; Animals ; Bronchial Hyperreactivity ; chemically induced ; Enzyme Inhibitors ; pharmacology ; Guanidines ; pharmacology ; Guinea Pigs ; Lipopolysaccharides ; toxicity ; Male ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide ; biosynthesis ; Nitric Oxide Synthase ; antagonists & inhibitors ; physiology

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

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