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Anti-N-methyl-D-aspartate receptor(NMDAR) encephalitis is a common autoimmune encephalitis.It is recognized gradually in neurological field in recent years.This disease has relatively consistent clinical manifestations.There is a specific anti-NMDAR antibody in cerebrospinal fluid,and a good response to immune therapy.Anti-NMDAR encephalitis is closely associated with viral encephalitis.It is often misdiagnosed as viral encephalitis before it is well understood.Recently,a number of studies have found that virus infection is an important inducing factor of anti-NMDAR encephalitis.The recurrence of the viral encephalitis,especially herpes simplex virus encephalitis,is partially caused by immunological reaction of the central nervous system secondary to virus infection,and the immunological therapy is necessary.The recognition of anti-NMDAR encephalitis and its relationship with viral encephalitis,is very important for the proper treatment and improving the outcome of the patients.
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<p><b>OBJECTIVE</b>To analyze the clinical characteristics and diagnosis of three cases with infant botulism.</p><p><b>METHOD</b>Clinical data of three clinically diagnosed cases with infant botulism in May 2015 in Peking University First Hospital were retrospectively analyzed. Literature search at databases of PubMed, Wanfang, China National Knowledge Infrastructure and VIP with the key words"infant AND botulism". The date of literature retrieval was from the database founding to November 2015. The characteristics of infant botulism were summarized through review of literature.</p><p><b>RESULT</b>Three patients were infants of 4-8 months of age, and all had acute onsets of anorexia and poor response. All of them had normal psychomotor development previously, and without clear history of exposure to poisons. The main findings on physical examination were reduced muscle strength and hypotonia, dullness or disappeared pupillary light reflex, reduced facial expression, weak crying and dysphagia. Unexpectedly their states of consciousness were relatively normal. Finally, through identification and PCR genotyping of bacteria in stool, 2 cases were confirmed as Clostridium (C.) botulinum type B infection. Totally 446 reports were retrieved from foreign language literature and 52 reports from Chinese literature. More than 3,000 cases of infant botulism cases were reported in the world. Rare cases were reported in China and only 1 case was reported in 2000.</p><p><b>CONCLUSION</b>Most cases of infant botulism had no clear exposure history. The main clinical manifestations are hypotonia, cranial nerve paralysis, flaccid paralysis, but different patients may have different presentations. Detection of C. Botulinum and its toxin in stool can help to confirm the diagnosis. Infant botulism is relatively rare in China, which may be related to the insufficient understanding and inspection level of the disease. It might be underestimated in China.</p>
Subject(s)
Humans , Infant , Botulism , China , Clostridium botulinum , Feces , Genotype , ParalysisABSTRACT
A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of H002 and its phosphorylated metabolite, H002-P and hydroxylated metabolite H002-M, in rat blood. H001, an analogue of H002, was used as the internal standard. Blood samples were prepared by simple protein precipitation. The analytes and internal standard were separated on a Zorbax SB-C18 column with a gradient mobile phase consisting of methanol and water containing 0.1% formic acid at a flow rate of 0.2 mL/min with an operating temperature of 20 °C. The detection was performed on a triple quadrupole tandem mass spectrometer with positive electrospray ionization in multiple-reaction monitoring mode. Linear detection responses were obtained from 0.2-100 ng/mL for H002 and H002-M, while 0.5-100 ng/mL for H002-P. The intra- and inter-day precision (RSD%) was within 11.76%, with the accuracy (RE%) ranging from -9.84% to 9.12%. The analytes were shown to be stable during sample storage, preparation and analytic procedures. The method was applied to determine the pharmacokinetics of H002 in rats, and a preliminary study showed that the pharmacokinetics of H002 correlated with its biological effect on peripheral blood lymphocytes.
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SUMMARY To demonstrate the clinical manifestation, diagnosis and treatment of myoclonus epilepsy with ragged-red-fibers ( MERRF) , a case of MERRF was presented with review of the literature. A 4-year-7-month-old girl was diagnosed with MERRF. She had tremor, fatigue and developmental delay for more than 2 years. Laboratory tests showed that the serum and urine lactic acid and pyruvic acid increased significantly. Electroencephalogram showed diffuse and focal spike slow wave and slow wave in right central and parietal regions. Electromyogram showed neurological damage. Gene mutational analysis showed mtDNA 8344 A>G mutation. The mutational rate was 78%. Mitochondrial disease MERRF syndrome was diagnosed. Cocktails therapy with vitamins B1, B6, B12, L-carnitine, and coenzyme Q10 was administra-ted to the patient. MERRF is a rare disease. The diagnosis can be made by gene mutational analysis. Cocktail therapy may slow down the deterioration of the disease. Gene therapy is still experimental.
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Organic anion transporting polypeptides (OATP), a member of solute carrier (SLC) superfamily, is considered as an important transmembrane uptake transporters. OATP is involved in the transport of a variety of endo- and xenobiotics (bile acids, bilirubin, prostaglandin, thyroid hormones, steroid hormone conjugates), drugs and toxins in a Na+ and ATP independent manner. Multiple factors (eg. hormones, proinflammatory cytokines, drugs) can affect the distribution, expression and activity of OATPs, leading to an altered accumulation of OATP substrates and related food-drug and drug-drug interactions. Changes in the distribution and expression of OATPs in malignant tissues may be related to the pathological process of cancer, while the modulation epigenetic mechanism also contributes to its distribution patterns. This review describes the factors that can affect the expression or function of OATPs, which may provide a valuable reference for drug development and the clarification of pathogenesis.
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Objective To develop a LC-MS/MS method for the quantification of TBI-166, a novel antituberculotic, in beagle dog plasma, and apply it to the pharmacokinetic and bioavailability study. Methods The preparation of plasma sample was a simple deproteinization by the addition of acetonitrile followed by centrifugation. The separation was performed on a Symmetry C 8 column (2.1 mm × 50 mm,3.5μm) with mobile phase of acetonitrile/water containing 0.1%formic acid(V/V) using a gradient elution mode at a flow rate of 0.2 ml/min. The detection was performed in positive selected reaction monitoring (SRM) mode with an electrospray ionization source. The analytes were quantified at m/z 590→478 for TBI-166 and m/z 260→183 for propranolol (internal standard, IS). Results Linear detection responses were obtained for TBI-166 in dog plasma ranging from 2 to 1000 ng/ml. The intra- and inter-day precisions (RSD%) were no more than 10%. The average recovery was greater than 98.6%, and there was good stability and no obvious matrix effect for the quantification. The method was successfully applied in the pharmacokinetic study of TBI-166 in beagle dogs. The AUC(0-t), Cmax and Tmax of TBI-166 in male and female dogs were(897.2±318.6) and(2615.1±1524.4) h·μg/L,(65.4±2.3) and(122.0±34.6) ng/ml and(1.4±0.5) and(4.4±3.5) h after oral administration at 3 mg/kg. The t1/2z, AUC(0-t), and CL of TBI-166 in male and female dogs were (69.6±35.3) and (112.9±25.3) h, (1798.0±729.2) and (3222.4±1656.2) h·μg/L,(0.2±0.1) and (0.3 ±0.1) L/(h·kg) after intravenous administration at 0.5 mg/kg. Conclusion An accurate, simple and sensitive LC-MS/MS method for the determination of TBI-166 in beagle dog plasma was developed and validated. This method was applied to the pharmacokinetic study of TBI-166 in beagle dogs. There was a gender difference on the pharmacokinetic profiles of TBI-166 in dogs. TBI-166 was eliminated slowly and the bioavailability of TBI-166 was 8.3-13.5% in male and female dogs.
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Objective:To explore the effect of bone marrow mesenchymal stem cell transplantation on silicosis fibrosis in different time windows in rats.Methods:BMSCs were isolated and cultured from male 3-week-old SD rats in vitro.Fifty healthy female SD rats were randomly divided into 5 groups:control group,silicosis model group,early treatment group,middle treatment group,late treatment group(n=10).The silicosis model was made by one-time infusion of silica dust suspension using the non-exposed tracheal in-tubation(50 μg/ml),and 1 d,14 d,28 d of BMSCs were given for intervention therapy (1 ×106 ml-1 ).Rats in each group were sacrificed 14 days after treatment.The BMSCs identified by flow cytometry;the morphological changes of the lung tissues were observed by HE staining;the expression of MMP-9,collagen type Ⅰ and collagen type Ⅲ were detected by immunocytochemistry and Western blot analysis.Results: BMSCs in early silicosis ( 1 d ) and the middle silicosis ( 14 d ) compared to silicosis model group can significantly alleviate the pathological process of silicosis fibrosis (P0.05).Conclusion:Exogenous BMSCs transplantation on rat silicosis early pathological processes play a role in delaying , late treatment effect is not obvious.
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Objective To observe expression of autophagy-related proteins LC-3 and Beclin-1 in alveolar macrophages in the silicosis model of rats , and to investigate the molecular mechanisms of silicosis formation from cells autophagy perspective .Methods Fifty adult male SD rats were randomly divided into control and model groups , 25 rats for each group .The silicosis model was made by one-time infusion of silica dust suspension through the trachea without exposed.The rats were sacrificed on the 1st, 3rd, 7th, 14th or 28th day after the modeling .Alveolar macrophages were obtained from bronchoalveolar lavage and used for subsequent research after culture and purification .Morphological characteristics of alveolar macrophages were observed by HE staining and transmission electron microscope ;The expression of LC-3 and Beclin-1 was detected by means of immunocytochemistry and Western blotting in each group .Results Compared with the control group , alveolar macrophages of the model group had larger volume and abundant cytoplasm , the phagocytic silica dust particles were observed in some cells , and autophagosomes were detected by transmission electron microscope .The expressions of LC-3 and Beclin-1 were increased at all time points in the model group ( P<0.05 ) .Both LC-3 and Beclin-1 began to increase at the 1st day.As the extension of time the expression gradually enhanced , peaked at the 14th day(P<0.05), and decreased at the 28th day, but higher than the basal expression .Conclusion Autophagy is activated in alveolar macrophages of the silicosis model , and alveolar macrophages autophagy is involved in the pathological process of silicosis in the rat .