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Reductions of astroglia expressing glial fibrillary acidic protein (GFAP) are consistently found in the prefrontal cortex (PFC) of patients with depression and in rodent chronic stress models. Here, we examine the consequences of PFC GFAP+ cell depletion and cell activity enhancement on depressive-like behaviors in rodents. Using viral expression of diphtheria toxin receptor in PFC GFAP+ cells, which allows experimental depletion of these cells following diphtheria toxin administration, we demonstrated that PFC GFAP+ cell depletion induced anhedonia-like behavior within 2 days and lasting up to 8 days, but no anxiety-like deficits. Conversely, activating PFC GFAP+ cell activity for 3 weeks using designer receptor exclusively activated by designer drugs (DREADDs) reversed chronic restraint stress-induced anhedonia-like deficits, but not anxiety-like deficits. Our results highlight a critical role of cortical astroglia in the development of anhedonia and further support the idea of targeting astroglia for the treatment of depression.
Assuntos
Anedonia , Astrócitos , Animais , Humanos , Astrócitos/metabolismo , Córtex Pré-Frontal/metabolismo , Depressão/metabolismo , Estresse Psicológico/metabolismo , Comportamento AnimalRESUMO
Apical and axillary buds of Guizotia abyssinica Cass., isolated from seedlings raised in vitro, were cultured. High frequency of shoot regeneration was achieved on MS medium with BAP (1 mgl(-1)). Effect of BAP, Kn and GA3 applied successively in culture on shoot regeneration and flower bud formation has been studied. The shoots differentiated in cultures elongated on this medium. These rooted subsequently on half strength MS medium. The shoots flowered in vitro on MS medium with a combination of BAP (0.1mgl(-1)) + GA3 (0.1 mgl(-1)). The plantlets thus formed were successfully hardened with 90 % survival.
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Identification is one of the most important aspects of mass disasters. Stature estimation is an essential parameter for identification and is widely used in forensic anthropology, where DNA facility is limited. A hand is most studied part of the upper limb; however, data are scarce concerning particular geographical populations. This study is an effort to provide tangible data for such forensic investigations. It was a prospective, cross-sectional study on 500 medicolegal death cases brought for post-mortem examination. It aimed to estimate stature in the Northwest population using hand and finger measurements of dead persons by mathematical models. A total of seven parameters in hand were used to generate linear and multiple regression equations, correlation coefficients and finger indexes for stature estimation and sex differentiation. The correlation coefficient between stature and all the hand measurements were significant except for the index and middle finger on both sides in females. Bilateral differences were insignificant for hand length and breath, except for the middle finger length in both sexes and length of thumb in females. Multiple regression equations for stature estimation were better than linear regression equations for stature estimation. SEE ranged from 4.31 to 6.26 in males and 4.11 to 5.25 in females. For identification, hand length is the best individual parameter among other hand measurements. The measurement accuracy and practical aspects can be enhanced if we consider cadaveric participants. The multiple regression model approach can give a fair estimate of the stature of the deceased.
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Mãos , Incidentes com Feridos em Massa , Masculino , Feminino , Humanos , Estudos Transversais , Estudos Prospectivos , Extremidade SuperiorRESUMO
Eight QSAR models (M1-M8) were developed from a dataset of 118 benzo-fused heteronuclear derivatives targeting VEGFR-2 by Monte Carlo optimization method of CORALSEA 2023 software. Models were generated with hybrid optimal descriptors using both SMILES and Graphs with zero- and first-order Morgan extended connectivity index from a training set of 103 derivatives. All statistical parameters for model validation were within the prescribed limits, establishing the models to be robust and of excellent quality. Among all models, split-2 of M5 was the best-fit as reflected by rvalidation2, Qvalidation2 and MAE. Mechanistic interpretation of this model assisted the identification of structural descriptors as promoters and hinderers for VEGFR-2 inhibition. These descriptors were utilized to design novel VEGFR-2 inhibitors (YS01-YS07) by bringing modifications in compound MS90 in the dataset. Docking of all designed compounds, MS90 and sorafenib with VEGFR-2 binding site revealed favourable binding interactions. Docking score of YS07 was higher than that of MS90 and sorafenib. Molecular dynamics simulation study revealed sustained interactions of YS07 with key amino acids of VEGFR-2 at a run time of 100 ns. This study concludes the development of a best fit QSAR model which can assist the design of new anticancer agents targeting VEGFR-2.
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Desenho de Fármacos , Simulação de Acoplamento Molecular , Relação Quantitativa Estrutura-Atividade , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/química , Simulação de Dinâmica Molecular , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Método de Monte Carlo , Simulação por ComputadorRESUMO
Reductions of astroglia expressing glial fibrillary acidic protein (GFAP) are consistently found in the prefrontal cortex (PFC) of patients with depression and in rodent chronic stress models. Here, we examine the consequences of PFC GFAP+ cell depletion and cell activity enhancement on depressive-like behaviors in rodents. Using viral expression of diphtheria toxin receptor in PFC GFAP+ cells, which allows experimental depletion of these cells following diphtheria toxin administration, we demonstrated that PFC GFAP+ cell depletion induced anhedonia-like behavior within 2 days and lasting up to 8 days, but no anxiety-like deficits. Conversely, activating PFC GFAP+ cell activity for 3 weeks using designer receptor exclusively activated by designer drugs (DREADDs) reversed chronic restraint stress-induced anhedonia-like deficits, but not anxiety-like deficits. Our results highlight a critical role of cortical astroglia in the development of anhedonia and further support the idea of targeting astroglia for the treatment of depression.
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An efficient protocol has been developed for regeneration of complete plants through somatic embryogenesis in H. coronarium. Creamish white, pale yellow and brown calli were obtained on MS medium supplemented with different concentrations of auxins [2, 4-Dichlorophenoxy acetic acid (2, 4-D), Indole-3 acetic acid (IAA) and 1-Naphthylacetic acid (NAA)] after 4 weeks. Creamy white calli developed on 0.5 mg L(-1) 2, 4-D turned embryogenic when subcultured on basal medium and produced small globular somatic embryos after 6 weeks. Further growth of somatic embryos required their transfer to medium containing 6-benzylaminopurine (BAP) or kinetin (KN). BAP was more effective than KN in promoting shoot proliferation. Maximum shoot length was obtained with 0.5 mg L(-1) BAP whereas maximum shoot number was obtained with 1.0 mg L(-1) BAP. The plantlets thus formed were successfully hardened, and transferred to sand-soil and farm yard manure (1:1:1) with 95% survival.
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Ácido 2,4-Diclorofenoxiacético/farmacologia , Técnicas de Embriogênese Somática de Plantas , Zingiberaceae/embriologia , Compostos de Benzil , Ácidos Indolacéticos/farmacologia , Cinetina/farmacologia , Ácidos Naftalenoacéticos/farmacologia , Reguladores de Crescimento de Plantas/farmacologia , Brotos de Planta/crescimento & desenvolvimento , Purinas , Zingiberaceae/efeitos dos fármacos , Zingiberaceae/crescimento & desenvolvimentoRESUMO
Clinical management protocols for COVID-19 are evolving rapidly as more information about the epidemiology and pathophysiological changes in COVID-19 become available. However, no definite treatment of COVID-19 has been found till date. The COVID-19 convalescent plasma (CCP) therapy has emerged as an important investigational therapy in the management of COVID-19 patients. Additionally, the regulatory agencies, in particular, the Indian blood transfusion council must release some interim recommendations for the blood centres on the CCP blood donor eligibility criteria after COVID-19 vaccination. More clinical trials are needed to know the efficacy of the CCP harvested from COVID-19 recovered individuals who have been vaccinated against those COVID-19 recovered individuals who are not vaccinated to understand the vaccine impact on the IgG titres of anti-SARS-CoV-2 antibodies.
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Anticorpos Antivirais/uso terapêutico , Segurança do Sangue , Vacinas contra COVID-19 , COVID-19/terapia , Seleção do Doador/normas , Imunoglobulina G/uso terapêutico , Pandemias , SARS-CoV-2/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/sangue , COVID-19/imunologia , Experimentação Humana , Humanos , Imunização Passiva/ética , Imunização Passiva/normas , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Consentimento Livre e Esclarecido , Proteínas Virais/imunologia , Soroterapia para COVID-19RESUMO
Depression is a neuropsychiatric disorder that affects more than 350 million people all over the world. There are psychological and pharmacological treatments for depression which mainly focus on monoaminergic neurotransmission theory. The main concern regarding available antidepressants is the lag period and other side effects, such as sexual dysfunction. Gepirone is a drug of the azapirone group which is a 5-HT1A receptor agonist belonging to the buspirone family. Gepirone is under clinical development and has been shown to be more effective than selective serotonin reuptake inhibitors (SSRIs), as this drug treats the psychiatric disorders without causing sexual dysfunction, which limits the use of SSRIs. It possesses greater selectivity for the 5-HT1A receptor than SSRIs. Clinical studies have shown that gepirone has differential action at pre- and postsynaptic 5-HT1A receptors. Gepirone extended-release tablets (gepirone ER, Travivo) showed promising effects in adult outpatients for the treatment of major depressive disorder (MDD) in a double-blind, randomized, placebo-controlled clinical study. Gepirone also showed an antianxiety effect in a placebo-controlled trial in generalized anxiety disorder. Absorption of gepirone is increased when administered with food as there is no substantial change in Cmax and half-life but it significantly increases AUC and mean residence time. Gepirone undergoes first-pass metabolism and its major metabolites are 1- (2-pyrimidinyl)-piperazine (1-PP) and 3-OH-gepirone, both of which are pharmacologically active. In addition to its better efficacy, gepirone is well tolerated and the major adverse effects observed have been nausea, dizziness and lightheadedness. Evidence from preclinical and clinical studies revealed that gepirone could be a breakthrough therapeutic agent in the treatment of anxiety and MDD.
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Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Pirimidinas/uso terapêutico , Agonistas do Receptor 5-HT1 de Serotonina/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoAssuntos
COVID-19 , Neoplasias , Medicina Transfusional , Idoso , Humanos , Oncologia , Neoplasias/terapia , PacientesAssuntos
COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , Doadores de Sangue , Humanos , Estudos SoroepidemiológicosRESUMO
PIP: A total of 23,084 deliveries were analyzed for 1 year. There was an overall incidence of 3.7% cases of preeclampsia with an overall predominance in primigravidas. There were 564 cases of mild preeclampsia with maximum occurrence in para 1-4, 260 cases of moderate preeclampsia with peak incidence in primigravidas, and 31 cases of severe preeclampsia also with peak incidence in primigravidas. The maximum occurrence in primigravidas in all forms of preeclampsia was in the age group 16-21 years of age. Almost 22.6% of those babies born to preeclamptic mothers weighed less than 2500 g whereas in 600 control normal uncomplicated pregnancies, only 4.67% of the babies were of that weight. 5.23% of the babies born from preeclamptic mothers were stillborn whereas the rate of stillbirth was nil in the 600 controls. 26.16% of the babies born of preeclamptic mothers had an Apgar score of less than 8, whereas only 8% of the 600 controls had an Apgar of less than 8. It was further analyzed that the birthweight of the babies and of the Apgar were inversely proportional to the degree of severity of preeclampsia in the mother. Also, the rate of stillbirths was directly proportional to the degree of severity of preeclampsia.^ieng
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Eclampsia/diagnóstico , Pré-Eclâmpsia/diagnóstico , Adolescente , Adulto , Índice de Apgar , Peso ao Nascer , Feminino , Humanos , Recém-Nascido , Quênia , Gravidez , PrognósticoRESUMO
PIP: The study is purpose was to identify the avoidable factors responsible for the high maternal mortality in the Pumwani Maternity Hospital in Nairobi, Kenya and to determine how the available facilities could be used to reduce the mortality. A retrospective study of maternal deaths was carried out at the hospital for the period 1975-1984. During this period, there were 223,111 births and 150 maternal deaths, giving an incidence of maternal mortality of 67.2/100,000 births. Eclampsia and severe preeclampsia, puerperal sepsis, ruptured uterus, and postpartum hemorrhage were among the leading causes of maternal deaths. The authors also concluded that the following factors contributed to the increased maternal mortality: high maternal age; primigravidy; grandmultiparity; lack of good antenatal, intranatal, and postnatal care; lack of investigations; lack of good transfusion services; lack of better skilled anesthetic staff; and lack of discipline among the medical personnel.^ieng
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Causas de Morte , Maternidades , Hospitais Especializados , Mortalidade Materna , Adulto , Feminino , Humanos , Quênia , Paridade , Cuidado Pré-NatalRESUMO
A community house to house survey to estimate the prevalence of paralytic poliomyelitis in children 5-15 years was undertaken from June to August, 1986 in the rural and urban field practice areas. The survey covered 96 and 93% of the houses in the rural and urban areas, respectively. Prevalence of lameness due to poliomyelitis among children aged 5-15 years was 3.5 in the rural and 2.7 in the urban area. Community health examination also confirmed that boys were more vulnerable than girls.
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Poliomielite/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Índia/epidemiologia , Masculino , Prevalência , População Rural , População UrbanaRESUMO
Brucellosis is a significant bacterial zoonotic disease with a high seroprevalence in low-to-middle-income countries where there is a significant contact of humans with animals. This prospective study was conducted to observe the seroprevalence of brucellosis in 75 symptomatic patients with pyrexia of unknown origin (PUO) and 75 high-risk individuals (10 veterinarians, 15 milkmen and 50 healthy contacts of symptomatic patients) with possible exposure to brucellosis. Serum samples collected from these patients and individuals were subjected to rose Bengal test (RBT) and ELISA for the detection of IgM and IgG antibodies. RBT was positive in 50 samples (40 PUO and 10 high risk), of which 25 (33.3%) PUO cases had detectable IgM antibodies, whereas IgG antibodies were detected in 20 patients. None of samples from high-risk individuals was reactive for IgM/IgG antibodies by ELISA. The overall seroprevalence in this study was 16.7% (33.3% in PUO patients). Being a predominantly livestock rearing area, brucellosis is a significant health-care problem in this part of India with this entity being linked to 33% of PUO cases.
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Flavonoids are substances which are widely distributed in the plant kingdom. They occur in considerable quantities in common food products, spices and beverages. Interest of researchers has been greatly enhanced towards therapeutic potential of flavonoids in last some years. This review summarizes important patents pertaining to recent biotechnological techniques applied for the production, analysis of biosynthetic pathways, effects and applications of different flavonoids. For systematic studies investigations which have been published in the form of patents, are classified in different sectors like biosynthesis, medical application, antimicrobial activity, alteration of flower color, industrial application, cosmetics, food and plant tissue culture. A number of activities have been observed in each sector with vast area of research on flavonoids.
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Antioxidantes/farmacologia , Flavonoides/biossíntese , Flavonoides/farmacologia , Antioxidantes/química , Vias Biossintéticas/fisiologia , Biotecnologia , Patentes como AssuntoRESUMO
A stability-indicating reversed-phase liquid chromatographic method has been developed and validated for simultaneous determination of losartan potassium and ramipril. Separations were achieved using a C(18) column with mobile phase consisting of acetonitrile and (0.2% v/v, pH 2.5) aqueous trifluoroacetic acid (45:55, v/v) in isocratic mode at 1 ml/min flow rate. Column effluent was monitored at 210 nm using a UV detector. The method was validated for selectivity, linearity, accuracy, precision, sensitivity and robustness. Novel microwave-assisted forced degradation technique was employed for evaluation of selectivity. The method demonstrated excellent linearity for losartan potassium and ramipril with regression coefficients of 0.9999 and 0.9998, respectively. The linearity range was found to be 62.5-5000 ng/ml and 125-10,000 ng/ml with the mean percentage recoveries of 100.36% (±2.27) and 100.16% (±3.33) for losartan potassium and ramipril, respectively. In a robustness study, a full factorial design revealed that the analytical response remains unaffected by small variations in the critical chromatographic factors. The method was found to be sensitive with quantification limits of 44.30 and 79.93 ng/ml for losartan potassium and ramipril. The method was successfully employed for the determination of losartan potassium and ramipril in commercially available and in-house prepared tablets.
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In this era of topical cataract surgeries, where patients come and get operated within 15-20 minutes and walk with 20/20 vision from the hospital, there is a nightmare for ophthalmologists which is called endophthalmitis and Toxic Anterior Segment Syndrome(TASS). Despite an uneventful surgery patient may land in ophthalmologist’s outpatient department with decreased vision the next day because of TASS. Mild cases respond to treatment but severe cases may end up losing vision and may require further intraocular surgeries. Thus, steps should be taken to prevent this monstrous disease from happening. This article reviews how to diagnose, treat and prevent TASS.