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1.
Neurol India ; 71(5): 923-927, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37929428

RESUMO

Background: A high dose of statin is used to obtain an intensive lipid-lowering in stroke patients, even in patients with normal lipid levels. There are limited data on effect of dosage of statins and functional outcome in stroke patients. Objectives: To compare serum cholesterol levels with severity of stroke measured by infarct volume. To compare functional outcome measured by mRS at day 90 with the dose of statin. Materials and Methods: This retrospective observational study was conducted in KMC Hospital Manipal, India between 2016 and 2018. Result: A total of 100 consecutive patients were included in the study, out of which 60 (60.0%) were males. Hyperlipidemia was present in 65 (65.0%) patients. On comparing the serum cholesterol levels with infarct volume using MRI, patients with low volume of ≤70 ml had higher mean serum total cholesterol concentration (223.83 mg/dl), whereas patients with high volume of >70 ml had low mean cholesterol level (218.70 mg/dl). The patients were divided into those who received low dose (≤20 mg) versus high dose (≥40 mg equivalent) of Atorvastatin. On comparing the mRS values at baseline and on day 90 with the dose of statins, patients who received a higher dosage had a statistically significant fall in mRS (p-0.045) at day 90. Conclusion: It was found that serum cholesterol levels were inversely related to the stroke severity. However, a higher the dose of statins resulted in better functional outcome and survival in post-stroke patients, possibly due to its neuroprotective effect.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , AVC Isquêmico , Acidente Vascular Cerebral , Masculino , Humanos , Feminino , Atorvastatina/uso terapêutico , Colesterol , Infarto , Resultado do Tratamento
2.
J Pediatr Genet ; 12(1): 76-80, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36684544

RESUMO

Introduction IQSEC2-related encephalopathy is an X-linked childhood neurodevelopmental disorder with intellectual disability, epilepsy, and autism. This disorder is caused by a mutation in the IQSEC2 gene, the product of which plays an important role in the development of the central nervous system. Case Report We describe the symptomatology, clinical course, and management of a 17-month-old male child with a novel IQSEC2 mutation. He presented with an atypical Rett syndrome phenotype with developmental delay, autistic features, midline stereotypies, microcephaly, hypotonia and epilepsy with multiple seizure types including late-onset infantile spasms. Spasms were followed by worsening of behavior and cognition, and regression of acquired milestones. Treatment with steroids led to control of spasms and improved attention, behavior and recovery of lost motor milestone. In the past 10 months following steroid therapy, child lags in development, remains autistic with no further seizure recurrence. Conclusion IQSEC2-related encephalopathy may present with Rett atypical phenotypes and childhood spasms. In resource-limited settings, steroids may be considered for spasm remission in IQSEC2-related epileptic encephalopathy.

3.
Curr Neurol Neurosci Rep ; 23(1): 1-14, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36445631

RESUMO

PURPOSE OF REVIEW: A variety of neurological complications have been reported following the widespread use of the COVID-19 vaccines which may lead to vaccine hesitancy and serve as a major barrier to the public health aim of achieving protective herd immunity by vaccination. In this article, we review the available evidence regarding these neurological adverse events reported, to provide clarity regarding the same so that unfounded fears maybe put to rest. RECENT FINDINGS: There is a greater than expected occurrence of severe neurological adverse events such as cortical sinus venous thrombosis, Bell's palsy, transverse myelitis, and Guillain-Barré syndromes along with other common effects such as headaches following different kinds of COVID-19 vaccination. Precipitation of new onset demyelinating brain lesions with or without detection of specific antibodies and worsening of pre-existing neurological disorders (like epilepsy, multiple sclerosis) are also a matter of great concern though no conclusive evidence implicating the vaccines is available as of now. The COVID-19 pandemic is far from being over. Till such time that a truly effective anti-viral drug is discovered, or an appropriate therapeutic strategy is developed, COVID-appropriate behavior and highly effective mass vaccination remain the only weapons in our armamentarium to fight this deadly disease. As often occurs with most therapeutic means for the treatment and prevention of any disease, vaccination against COVID-19 has its hazards. These range from the most trivial ones like fever, local pain and myalgias to several potentially serious cardiac and neurological complications. The latter group includes conditions like cerebral venous thrombosis (curiously often with thrombocytopenia), transverse myelitis and acute inflammatory demyelinating polyneuropathy amongst others. Fortunately, the number of reported patients with any of these serious complications is far too low for the total number of people vaccinated. Hence, the current evidence suggests that the benefits of vaccination far outweigh the risk of these events in majority of the patients. As of now, available evidence also does not recommend withholding vaccination in patients with pre-existing neurological disorders like epilepsy and MS, though adenoviral vaccines should be avoided in those with history of thrombotic events.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Síndrome de Guillain-Barré , Mielite Transversa , Trombose Venosa , Humanos , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Síndrome de Guillain-Barré/epidemiologia , Síndrome de Guillain-Barré/etiologia , Pandemias , Vacinação/efeitos adversos
4.
J Neurol Neurosurg Psychiatry ; 93(12): 1299-1305, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36376023

RESUMO

BACKGROUND: High-level evidence for using steroids in epileptic encephalopathy (EE), other than West syndrome (WS), is lacking. This study investigated the efficacy and safety of pulse intravenous methylprednisolone (IVMP) in EE other than WS. METHODS: This is an open-label evaluator-blinded randomised controlled study. Children aged 6 months or more with EE other than WS were included. Eighty children were randomised into intervention and non-intervention groups with 40 in each group. At the first visit (T1) seizure frequency, electroencephalographic (EEG) and Vineland Social Maturity Scale (VSMS) were obtained, and antiseizure medication (ASM) were optimised. After 1 month (T2), subjects were randomised to intervention (ASM+3 months IVMP pulse) or non-intervention group (only ASM) with 40 subjects in each group. They were followed up for 4 months (T3) and assessed. RESULTS: After 4 months of follow-up, 75% of patients receiving IVMP had >50% seizure reduction versus 15.4% in control group (χ2=28.29, p<0.001) (RR 4.88, 95% CI 2.29 to 10.40), median percentage change in seizure frequency (91.41% vs 10%, p<0.001), improvement in EEG (45.5% vs 9.4%, χ2=10.866, p=0.001) and social age domain of VSMS scores (Z=-3.62, p<0.001) compared with baseline. None of the patients in the intervention group had any serious side-effects. DISCUSSION: Three-month pulse IVMP therapy showed significant improvement in seizure frequency, EEG parameters and VSMS scores, with no steroid-related serious adverse effects. It can be considered as a safe and effective add on treatment in children with EE other than WS. TRIAL REGISTRATION NUMBER: CTRI/2019/02/017807.


Assuntos
Encefalopatias , Metilprednisolona , Criança , Humanos , Metilprednisolona/efeitos adversos , Convulsões/terapia , Resultado do Tratamento , Administração Intravenosa
5.
Epilepsy Behav ; 137(Pt A): 108946, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36379187

RESUMO

OBJECTIVE: Eating epilepsy presents various imaging and electrophysiological features along with various seizure triggers. As such, network changes in eating epilepsy have not been comprehensively explored. This study was conducted to illustrate resting state network changes in eating epilepsy and to study the changes in network configurations during eating. METHODS: Magnetoencephalography recordings of nineteen patients with drug-resistant eating epilepsy were compared with healthy controls during resting state. A subgroup of nine patients and 12 controls had MEG recordings during eating. Network changes were analyzed using phase lag index across 5 frequency bands [delta, theta, alpha, beta, and gamma] using clustering coefficient (CC), betweenness centrality (BC), path length (PL), modularity (Q), and small worldness (SW). RESULTS: During the resting state, PL was decreased in patients with epilepsy in the delta, theta, and gamma band. Q was lower in patients with epilepsy in the beta and gamma bands. During eating, in patients with epilepsy, PL and SW were increased in all frequency bands, and Q was decreased in the beta band and increased in the rest of the frequency bands. Patients with mixed types of seizures showed higher PL in all bands except alpha, higher Q in all bands, and higher SW in the alpha and beta bands. Node-wise changes in CC and BC implicated changes in DMN and 'eating' networks. CONCLUSION: Reflex Eating epilepsy presents with a hyperconnected network that exacerbates during eating. The cause of seizure onset and loss of consciousness in eating epilepsy might be due to aberrant network interaction between the regions of the brain involved with eating, such as the sensorimotor cortex, lateral parietal cortex, and insula with the limbic cortex and default mode network across multiple frequency bands.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia Reflexa , Humanos , Magnetoencefalografia/métodos , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Convulsões
6.
Am J Physiol Renal Physiol ; 323(2): F156-F170, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35695380

RESUMO

The lysosomal storage disease cystinosis is caused by mutations in CTNS, encoding the cystine transporter cystinosin, and in its severest form leads to proximal tubule dysfunction followed by kidney failure. Patients receive the drug-based therapy cysteamine from diagnosis. However, despite long-term treatment, cysteamine only slows the progression of end-stage renal disease. Preclinical testing in cystinotic rodents is required to evaluate new therapies; however, the current models are suboptimal. To solve this problem, we generated a new cystinotic rat model using CRISPR/Cas9-mediated gene editing to disrupt exon 3 of Ctns and measured various parameters over a 12-mo time course. Ctns-/- rats display hallmarks of cystinosis by 3-6 mo of age, as demonstrated by a failure to thrive, excessive thirst and urination, cystine accumulation in tissues, corneal cystine crystals, loss of LDL receptor-related protein 2 in proximal tubules, and immune cell infiltration. High levels of glucose, calcium, albumin, and protein were excreted at 6 mo of age, consistent with the onset of Fanconi syndrome, with a progressive diminution of urine urea and creatinine from 9 mo of age, indicative of chronic kidney disease. Kidney histology and immunohistochemistry showed proximal tubule atrophy and glomerular damage as well as classic "swan neck" lesions. Overall, Ctns-/- rats show a disease progression that more faithfully recapitulates nephropathic cystinosis than existing rodent models. The Ctns-/- rat provides an excellent new rodent model of nephropathic cystinosis that is ideally suited for conducting preclinical drug testing and is a powerful tool to advance cystinosis research.NEW & NOTEWORTHY Animal models of disease are essential to perform preclinical testing of new therapies before they can progress to clinical trials. The cystinosis field has been hampered by a lack of suitable animal models that fully recapitulate the disease. Here, we generated a rat model of cystinosis that closely models the human condition in a timeframe that makes them an excellent model for preclinical drug testing as well as being a powerful tool to advance research.


Assuntos
Sistemas de Transporte de Aminoácidos Neutros , Cistinose , Síndrome de Fanconi , Sistemas de Transporte de Aminoácidos Neutros/genética , Sistemas de Transporte de Aminoácidos Neutros/metabolismo , Animais , Cisteamina/farmacologia , Cisteamina/uso terapêutico , Cistina/genética , Cistina/metabolismo , Cistina/uso terapêutico , Cistinose/tratamento farmacológico , Cistinose/genética , Cistinose/metabolismo , Síndrome de Fanconi/genética , Fenótipo , Ratos
7.
Epilepsy Res ; 178: 106804, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34753071

RESUMO

BACKGROUND: Parieto-occipital (PO) gliosis secondary to perinatal insult, is often associated with neurologic sequelae such as epilepsy, which can be drug resistant. OBJECTIVE: To evaluate the spectrum of epilepsy among patients presenting with seizures in association with PO gliosis and to determine factors that influence the development of epileptic encephalopathy (EE) in these patients. METHODS: We retrospectively evaluated patients aged < 16 years with drug refractory epilepsy and PO gliosis who underwent video electroencephalography (Video EEG). We evaluated the clinical, electrophysiological and radiological profile including treatment responsiveness of subjects with EE. RESULTS: One hundred one patients (M: F=3:1) with mean age of onset of epilepsy at 28.9 ± 33.1 months were recruited into the study. Based on video EEG findings, Based on video EEG findings, the commonest type of focal onset ictus was tonic seizures with impaired awareness (n = 26, 29.9%). Myoclonic jerks (n = 20, 23%) were the commonest type of generalised onset seizures. Ictal onset from parieto occipital region were observed in 28 patients. Ictal onset from frontal, temporal and fronto temporal region were observed in 6 (6.8%), 7(7.9%) and 9 (8.9%) patients, respectively. Comparison of the seizure types and ictal onset among subgroups of patients with occipital gliosis, parieto-occipital gliosis and parieto-occipital with frontal gliosis revealed that the extent of gliosis did not significantly affect seizure semiology or ictal onset. EE was significantly associated with presence of neonatal seizures (p = 0.04), hypoglycaemia (p = 0.005), longer duration of ICU stay (Z score = -3.55, p < 0.001) and younger age of onset of seizures (Z score = - 2.97, p = 0.03). Eleven out of eighteen (64.7%) subjects with EE showed greater than 50% improvement in seizure frequency following three months of pulse intravenous methylprednisolone therapy. CONCLUSIONS: Among subjects with PO gliosis on MRI, the seizure semiology is unaffected by laterality, radiologic extension beyond the occipital cortex or presence of ulegyria. Patients with PO gliosis can have florid interictal epileptiform discharges anteriorly and can have seizures with ictal onset from frontal and temporal region. Development of EE is strongly related to the age of onset of seizures, neonatal seizures, prolonged NICU admission, rather than the radiological findings. Subjects with EE and PO gliosis show good response to intravenous pulse methylprednisolone.


Assuntos
Epilepsia Resistente a Medicamentos , Adolescente , Criança , Pré-Escolar , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Eletroencefalografia , Gliose/diagnóstico por imagem , Humanos , Recém-Nascido , Estudos Retrospectivos , Convulsões/diagnóstico por imagem , Convulsões/tratamento farmacológico
8.
Neurol India ; 69(2): 480-482, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33904481

RESUMO

Melioidosis is an under recognized infectious disease which may rarely present with neurological involvement. Neurological melioidosis has protean manifestations, and in this case series we present 3 patients diagnosed from a single center in southern India. The clinical presentation of the patients we describe includes rhomb-encephalitis, scalp infection with subdural and meningeal involvement, and optic neuritis associated with pulmonary melioidosis. We discuss the possible mechanism of involvement of the nervous system, and the recommended treatment. Diagnosis of melioidosis requires a high index of suspicion and should be considered in endemic areas. Through this series we hope to improve the awareness of this infection and its neurological presentation.


Assuntos
Melioidose , Meningite , Neurite Óptica , Abscesso , Humanos , Índia , Melioidose/complicações , Melioidose/diagnóstico , Melioidose/tratamento farmacológico , Meningite/diagnóstico , Meningite/etiologia , Neurite Óptica/diagnóstico , Neurite Óptica/etiologia , Couro Cabeludo
9.
Epilepsy Res ; 173: 106611, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33740698

RESUMO

OBJECTIVES: To study the effect of monthly pulses of intravenous methylprednisolone (IVMP) on seizure and global outcomes in children with epileptic encephalopathy (EE). METHODS: This retrospective study was undertaken in a tertiary care epilepsy center in India. Consecutive patients with EE who had received IVMP as adjunctive therapy for a minimum of 3 months and had at least one pre-and post-steroid EEG each, were identified and a structured questionnaire was used to collect information including outcomes at 3 months post-steroid course completion and beyond, as available. RESULTS: Ninety-seven patients (M:F=71:26) fulfilling the inclusion criteria with a mean age at onset of seizures being 20.52 ± 25.69 months were included. Commonest seizure types were myoclonic (66%); Lennaux-Gastaut and West Syndromes accounted for 57 % and 24 % patients respectively. The etiology was unknown in 52 %. All children were on a combination of standard anti-seizure drugs. The duration of IVMP pulse therapy was 7.72 ± 6.25 months. One-fourth (26 %) patients experienced minor adverse events. Greater than 50 % seizure burden reduction was seen in 66 % patients at 3 months with seizure-freedom in 25 %. A total of 45 (46 %) patients became seizure-free in the cohort eventually with continuation of steroids beyond 3 months. Children with idiopathic EEs, normal neuroimaging, myoclonic jerks, and West syndrome showed the best response. The presence of burst-suppression and generalized paroxysmal fast activity (GPFA) predicted inadequate response. CONCLUSIONS: Adjunct pulse doses of IVMP are safe, well-tolerated, and effective in reducing seizures and improving global outcomes in children with idiopathic EEs, West syndrome, normal neuroimaging, and myoclonic jerks. Seizure freedom might be delayed in a subset of these patients, hence duration of therapy beyond 3 months may be warranted.


Assuntos
Epilepsia , Espasmos Infantis , Criança , Eletroencefalografia , Epilepsia/tratamento farmacológico , Humanos , Metilprednisolona/uso terapêutico , Estudos Retrospectivos , Espasmos Infantis/tratamento farmacológico
12.
Epilepsy Behav ; 110: 107173, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32619961

RESUMO

OBJECTIVE: The objective of this study was to describe the socioeconomic consequences of drug-resistant epilepsy (DRE). METHODS: This study comprised 132 (equal males and females) consecutive patients aged ≥18 years, who fulfilled the International League Against Epilepsy (ILAE) definition for DRE, prospectively seen in a tertiary care center in South India. We used a structured questionnaire to gather relevant information. RESULTS: The mean age was 31 (range 18-70) years. Mean age of onset of epilepsy was 17 years and mean duration of epilepsy 14 years. The most common epilepsy type and etiology were focal epilepsy and gliotic lesions secondary to perinatal insults, respectively. The average out of the pocket expenditure on antiseizure drugs annually amounted to 19% of the gross national product (GNP)/capita, which was borne by family members in more than two-thirds of the subjects. Almost 60% reported epilepsy having affected their education, 40% their employment, and 90% their marital prospects. Female patients were less often employed outside their homes and had more marital problems compared with males. CONCLUSIONS: In addition to high seizure burden, DRE adversely affects the pursuit of higher education, employment, and marriage. Besides the direct cost of epilepsy, these issues augment both the patient and the caregiver's liability. Socioeconomic consequences of DRE are widely prevalent in developing countries, and this study highlights the need to address them.


Assuntos
Epilepsia Resistente a Medicamentos/economia , Epilepsia Resistente a Medicamentos/epidemiologia , Escolaridade , Fatores Socioeconômicos , Adolescente , Adulto , Idoso , Estudos de Coortes , Epilepsia Resistente a Medicamentos/terapia , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Centros de Atenção Terciária/economia , Centros de Atenção Terciária/tendências , Adulto Jovem
14.
Acta Neuropathol ; 139(1): 135-156, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31535203

RESUMO

Multiple system atrophy (MSA) is a fatal late-onset neurodegenerative disease. Although presenting with distinct pathological hallmarks, which in MSA consist of glial cytoplasmic inclusions (GCIs) containing fibrillar α-synuclein in oligodendrocytes, both MSA and Parkinson's disease are α-synucleinopathies. Pathologically, MSA can be categorized into striatonigral degeneration (SND), olivopontocerebellar atrophy (OPCA) or mixed subtypes. Despite extensive research, the regional vulnerability of the brain to MSA pathology remains poorly understood. Genetic, epigenetic and environmental factors have been proposed to explain which brain regions are affected by MSA, and to what extent. Here, we explored for the first time epigenetic changes in post-mortem brain tissue from MSA cases. We conducted a case-control study, and profiled DNA methylation in white mater from three brain regions characterized by severe-to-mild GCIs burden in the MSA mixed subtype (cerebellum, frontal lobe and occipital lobe). Our genome-wide approach using Illumina MethylationEPIC arrays and a powerful cross-region analysis identified 157 CpG sites and 79 genomic regions where DNA methylation was significantly altered in the MSA mixed-subtype cases. HIP1, LMAN2 and MOBP were amongst the most differentially methylated loci. We replicated these findings in an independent cohort and further demonstrated that DNA methylation profiles were perturbed in MSA mixed subtype, and also to variable degrees in the other pathological subtypes (OPCA and SND). Finally, our co-methylation network analysis revealed several molecular signatures (modules) significantly associated with MSA (disease status and pathological subtypes), and with neurodegeneration in the cerebellum. Importantly, the co-methylation module having the strongest association with MSA included a CpG in SNCA, the gene encoding α-synuclein. Altogether, our results provide the first evidence for DNA methylation changes contributing to the molecular processes altered in MSA, some of which are shared with other neurodegenerative diseases, and highlight potential novel routes for diagnosis and therapeutic interventions.


Assuntos
Metilação de DNA/genética , Proteínas de Ligação a DNA/genética , Lectinas de Ligação a Manose/genética , Proteínas de Membrana Transportadoras/genética , Atrofia de Múltiplos Sistemas/genética , Proteínas da Mielina/genética , Idoso , Encéfalo/metabolismo , Encéfalo/patologia , Estudos de Casos e Controles , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/patologia , Substância Branca/metabolismo , Substância Branca/patologia , alfa-Sinucleína/genética
15.
J Stroke Cerebrovasc Dis ; 28(3): 807-814, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30554938

RESUMO

BACKGROUND: Sleep apnea is increasingly being recognized as 1 of the important, modifiable risk factors of stroke and cardiovascular diseases. Sleep apnea is thought to impair the functional recovery following stroke. Hence, we evaluated the patients with acute ischemic stroke for prevalence of sleep apnea and compared the functional outcomes of patients with and without sleep apnea, at 3rd month of acute ischemic stroke. METHOD: This study was conducted in Kasturba Medical College (KMC) hospital, Manipal, India, between May 2015 and August 2016. We included 102 consecutive patients of acute ischemic stroke with hemiplegic upper limb power of Medical Research Council (MRC) 3 or less. Sleep apnea was diagnosed in these patients using the sleep disordered Questionnaire, Berlin Questionnaire, and Epworth sleepiness scale. Functional outcome was measured using Barthel score on day 7 and at 3rd month following the onset of stroke. RESULT: Out of 102 patients, sleep apnea was present in 31 (30.6%) patients, more in males (67.7%) and elderly. Hypertension was present in 66.6% of patients with sleep apnea. NIHSS score at admission did not differ between the 2 groups. At 3rd month, the Barthel score calculated was better among patient with no apnea, but this was not statistically significant (P = .119). When mean Barthel score at baseline and 3rd month was calculated using repeated measure Analysis of Variance (ANOVA) between the 2 groups, gain in functional independence in no apnea group was statistically significant (P < .001). CONCLUSION: Sleep-disordered breathing is an independent risk factor for stroke, and sleep apnea is also associated with other known stroke risk factors like hypertension. In acute ischemic stroke, sleep apnea has a negative impact on functional recovery. Sleep apnea is amenable to treatment and should be considered in patients with acute ischemic stroke to improve the chance of recovery, and to reduce the risk of recurrence.


Assuntos
Isquemia Encefálica/fisiopatologia , Síndromes da Apneia do Sono/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Adulto , Idoso , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/terapia , Avaliação da Deficiência , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Prospectivos , Recuperação de Função Fisiológica , Fatores de Risco , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/terapia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Inquéritos e Questionários , Fatores de Tempo
16.
Risk Manag Healthc Policy ; 11: 243-250, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30584380

RESUMO

PURPOSE: To determine morbidity and mortality of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) infections in a tertiary health care facility. METHODS: A cohort study among hospitalized adult patients with culture proven MRSA or MSSA monoinfection were recruited in a tertiary referral center in South India from November 2011 to December 2012. RESULTS: Of total 551 subjects, 284 (52%) had MRSA and 267 (48%) MSSA infection. A total of 184 (65%) subjects had health care-associated MRSA (HA-MRSA) and 100 (35%) community-associated MRSA (CA-MRSA). Chronic kidney disease and recent antibiotic use had significant association with MRSA. MRSA patients had significant respiratory infection (OR 2.24 [1.04, 5.16]) and bacteremia (OR 2.24 [10.40, 5.16]), relative to MSSA. MSSA group had better survival function compared to MRSA group (P=0.028). Median duration of ICU stays were 5 days (IQR 4, 8) and 2 days (IQR 2, 2) in MRSA and MSSA, respectively. Complications such as acute kidney injury, sepsis, multiorgan dysfunction, need for supportive measures were more in the MRSA group. CONCLUSION: MRSA imposes a huge burden in Indian scenario and HA-MRSA remains the main culprit. Patients with history of chronic kidney disease and recent use of antibiotics were found to be at a higher risk. Patients with MRSA infections tend to have poorer outcomes in terms of longer hospital stay, greater complications, and mortality.

18.
Biotechnol Prog ; 33(3): 726-736, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28371174

RESUMO

OBJECTIVE: For efficient biofarming we attempted to enrich plant interstitial fluid (IF)/apoplastic fluid with targeted recombinant therapeutic protein. We employed a synthetic human Glucocerebrosidase (GCB), a model biopharmaceutical protein gene in this study. RESULTS: Twenty one Nicotiana varieties, species and hybrids were initially screened for individual IF recovery and based on the findings, we selected Nicotiana tabacum NN (S-9-6), Nicotiana tabacum nn (S-9-7) and Nicotiana benthamiana (S-6-6) as model plants for raising transgenic expressing GCB via Agrobacterium mediated transformation under the control of M24 promoter; GCB specific activity in each transgenic lines were analyzed and we observed higher concentration of recombinant GCB in IF of these transgenic lines (S-9-6, S-9-7, and S-6-6) in comparison to their concentration in crude leaf extracts. CONCLUSION: Recovery of valuable therapeutics in plant IF as shown in the present study holds great promise for promoting plant based biofarming. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:726-736, 2017.


Assuntos
Glucosilceramidase/metabolismo , Extratos Vegetais/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Glucosilceramidase/genética , Humanos , Extratos Vegetais/genética , Folhas de Planta/química , Plantas Geneticamente Modificadas/genética , Regiões Promotoras Genéticas/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Nicotiana/metabolismo
19.
PLoS Negl Trop Dis ; 11(2): e0005382, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28182670

RESUMO

BACKGROUND: Blindness is caused by eye pathogens that include a free-living protist (Acanthamoeba castellanii, A. byersi, and/or other Acanthamoeba spp.), a fungus (Fusarium solani), and a bacterium (Chlamydia trachomatis). Hand-eye contact is likely a contributor to the spread of these pathogens, and so hand washing with soap and water or alcohol-based hand sanitizers (when water is not available) might reduce their transmission. Recently we showed that ethanol and isopropanol in concentrations present in hand sanitizers kill walled cysts of Giardia and Entamoeba, causes of diarrhea and dysentery, respectively. The goal here was to determine whether these alcohols might kill infectious forms of representative eye pathogens (trophozoites and cysts of Acanthamoeba, conidia of F. solani, or elementary bodies of C. trachomatis). METHODOLOGY/PRINCIPAL FINDINGS: We found that treatment with 63% ethanol or 63% isopropanol kills >99% of Acanthamoeba trophozoites after 30 sec exposure, as shown by labeling with propidium iodide (PI) and failure to grow in culture. In contrast, Acanthamoeba cysts, which contain cellulose fibers in their wall, are relatively more resistant to these alcohols, particularly isopropanol. Depending upon the strain tested, 80 to 99% of Acanthamoeba cysts were killed by 63% ethanol after 2 min and 95 to 99% were killed by 80% ethanol after 30 sec, as shown by PI labeling and reduced rates of excystation in vitro. Both ethanol and isopropanol (63% for 30 sec) kill >99% of F. solani conidia, which have a wall of chitin and glucan fibrils, as demonstrated by PI labeling and colony counts on nutrient agar plates. Both ethanol and isopropanol (63% for 60 sec) inactivate 96 to 99% of elementary bodies of C. trachomatis, which have a wall of lipopolysaccharide but lack peptidoglycan, as measured by quantitative cultures to calculate inclusion forming units. CONCLUSIONS/SIGNIFICANCE: In summary, alcohols kill infectious forms of Acanthamoeba, F. solani, and C. trachomatis, although longer times and higher ethanol concentrations are necessary for Acanthamoeba cysts. These results suggest the possibility that expanded use of alcohol-based hand sanitizers in places where water is not easily available might reduce transmission of these important causes of blindness.


Assuntos
2-Propanol/farmacologia , Acanthamoeba castellanii/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Chlamydia trachomatis/efeitos dos fármacos , Etanol/farmacologia , Fusarium/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Viabilidade Microbiana/efeitos dos fármacos , Fatores de Tempo
20.
Antimicrob Agents Chemother ; 59(11): 6749-54, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26282413

RESUMO

Enteric protozoan parasites, which are spread by the fecal-oral route, are important causes of diarrhea (Giardia duodenalis) and amebic dysentery (Entamoeba histolytica). Cyst walls of Giardia and Entamoeba have a single layer composed of fibrils of ß-1,3-linked GalNAc and ß-1,4-linked GlcNAc (chitin), respectively. The goal here was to determine whether hand sanitizers that contain ethanol or isopropanol as the active microbicide might reduce transmission of these parasites. We found that treatment with these alcohols with or without drying in a rotary evaporator (to model rapid evaporation of sanitizers on hands) kills 85 to 100% of cysts of G. duodenalis and 90 to 100% of cysts of Entamoeba invadens (a nonpathogenic model for E. histolytica), as shown by nuclear labeling with propidium iodide and failure to excyst in vitro. Alcohols with or without drying collapsed the cyst walls of Giardia but did not collapse the cyst walls of Entamoeba. To validate the in vitro results, we showed that treatment with alcohols eliminated oral infection of gerbils by 1,000 G. duodenalis cysts, while a commercial hand sanitizer (Purell) killed E. invadens cysts that were directly applied to the hands. These results suggest that expanded use of alcohol-based hand sanitizers might reduce the transmission of Giardia and Entamoeba.


Assuntos
Entamoeba/patogenicidade , Giardia/patogenicidade , Higienizadores de Mão/uso terapêutico , 2-Propanol/farmacocinética , 2-Propanol/uso terapêutico , Animais , Entamoeba/efeitos dos fármacos , Etanol/farmacologia , Etanol/uso terapêutico , Feminino , Gerbillinae , Giardia/efeitos dos fármacos , Giardíase/tratamento farmacológico , Giardíase/fisiopatologia , Higienizadores de Mão/farmacologia
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