Good Clinical Practice (GCP) – an alternative, unarticulated narrative

GCP has become the gold-standard for clinical research; initiated as a guideline pertaining to new drug development, it became a law in many countries, extending its scope to include all research. GCP is an excellent document that outlines the responsibilities of stakeholders involved in clinical research. Widely acclaimed, and deservedly so, it is considered as the “go-to” document whenever questions arise during the conduct of a clinical trial. This article presents another narrative, one that has not been articulated so far. Irrespective of whether we consider GCP as a law or a guideline, it is viewed as an “official” document, without the overt realisation that this was actually an initiative of the pharmaceutical industry, the “masters of mankind”. While the stress on documentation and monitoring in GCP was justified, its over-interpretation led to increased costs of clinical trials, with the result that smaller companies find it difficult to conduct the already expensive trials. GCP as an idea is now so entrenched within the scientific community that the real aims which led to its birth and that can be mined from the ICH website, like the need for market expansion, have remained largely unnoticed and undocumented, and are being expressed here.

Role of External Ventricular Drainage (EVD) in Treating Spontaneous Intraventricular Haemorrhage

Background: There is no consensus in the literature on the effects of the development of hydrocephalus on survival and disability after intracerebral haemorrhage (ICH) and the benefits of external ventricular drainage (EVD). This study is planned to describe the role of external ventricular drainage in treating patients of spontaneous, either primary or secondary, intraventricular haemorrhage with hydrocephalus.Material & Methods:A hospital based prospective interventional study was conducted in the Department of Neurosurgery of Dhaka Medical College Hospital, which is a tertiary level hospital, from April 2016 to September 2017.Total 42 patients of spontaneous intraventricular haemorrhage, either primary or secondary, with hydrocephalus were selected for this study. All the collected data were entered into IBM SPSS software, Version 24. For statistical analysis, paired t-test to compare the preoperative GCS with postoperative GCS at 24 hours was done.Results:Among 42 patients, age range was 26-75 years with the mean age 65.2 � 10.87 years. Male were 26 (61.9%) and female were 16 (38.1%). Male-Female ratio was 1.625:1. No patient needed conversion of EVD into VP shunt. EVD drain became blocked in 5 cases which were managed accordingly. 5 patients developed ventriculitis among which 2 patients died and rest 3 improved with antibiotics.Conclusions:The results of present study shows that EVD has a good role in the treatment of spontaneous IVH with hydrocephalus when ICH volume is low (<30ml) and modified Graeb Score is low (?10 found in this in this study. Preoperative higher GCS or initial improvement in GCS or initial improvement in GCS at 24 hours positively correlates with Glasgow outcome scale which is an indication of good function outcome.

The analytical procedure for determination of Assay in finished product of Clofarabine Injection, 1mg/mL is an In-House procedure.

A new and stability-indicating High performance liquid chromatographymethod was developed and validated for simultaneous determination of clofarabine impurities in Injectionformulation.The Chromatographic system consisted of a Shimadzu Class VP Binary pump LC-10ATvp, SIL-10ADvp Auto sampler, CTO-10Avp Column Temperature Oven, SPD-10Avp UV-Visible Detector.The method was validated as per the ICH guidelines Apart from these Chromatographic parameters likeresolution, capacity factor, separation factor, column efficiency and peakasymmetry should also be the ideal for estimation.

Determinación de los factores de mal pronóstico de la hemorragia intracerebral espontánea / Determination of poor prognosis factors of spontaneous intracerebral hemorrhage

Introducción: Las enfermedades cerebrovasculares son un problema de salud mundial. Estas constituyen la tercera causa de muerte, la primera de discapacidad en el adulto y la segunda de demencia en el planeta. Dentro ella, la hemorragia intracerebral espontánea es la segunda causa más común de enfermedad cerebrovascular, y llega a ser la tercera causa de muerte en Cuba. Objetivos: Determinar los principales factores de mal pronóstico que influyen en la evolución de los pacientes con la hemorragia intraparenquimatosa espontánea. Métodos: Se realizó un estudio observacional, transversal de una muestra conformada por pacientes atendidos en el Servicio de Neurología provincial de Camagüey, con diagnóstico de hemorragia cerebral espontánea primaria, confirmada por tomografía axial. Resultados: En esta investigación se detectó el predominio de hombres mayores de 80 años, con afectación de leve a moderada del estado de conciencia, predominaron las lesiones supratentoriales, y pocos casos con evacuación ventricular y sí un elevado porcentaje de hemorragias superiores a los 30 mL, con predominio de hipertensión arterial. Conclusiones: La mortalidad al alta hospitalaria no fue elevada, muy relacionada con la escala ICH(AU)

Introduction: Cerebrovascular diseases are a global health problem. These constitute the third cause of death, the first of disability in adults and the second of dementia on the planet. Within it, spontaneous intracerebral hemorrhage is the second most common cause of cerebrovascular disease, and it becomes the third cause of death in Cuba. Objectives: To determine the main factors of poor prognosis that influence the evolution of patients with spontaneous intraparenchymal hemorrhage. Methods: An observational, cross-sectional study was carried out of a sample made up of patients treated at Camagüey provincial Neurology service, with a diagnosis of primary spontaneous cerebral hemorrhage, confirmed by axial tomography. Results: In this research, a predominance of men over 80 years of age was detected, with mild to moderate impairment of the state of consciousness, supratentorial lesions predominated, and few cases with ventricular evacuation and high percentage of hemorrhages greater than 30 cc , with predominance of arterial hypertension. Conclusions: Mortality at hospital discharge was not high, closely related to the ICH score(AU)

The clinical profile of patients with intracerebral hemorrhage after receiving acute coronary syndrome regimen in a tertiary hospital: A case series

@#Coronary heart disease, which includes acute coronary syndromes (ACS) is a major cause of death and morbidity. Treatment for this condition includes dual anti-platelet treatment combined with an anti-coagulant and an anti-dyslipidemic. Bleeding complications may occur and one fatal adverse event is intracerebral hemorrhage (ICH). ACS cases in a tertiary hospital for the years 2014-2018 showed that there were 7 patients who presented with symptomatic ICH after treatment administration that accounts for 0.01% of a total of 1,097 patients. These patients were over the age of 50, but with no sex predilection. Common comorbidities were hypertension and malignancy. All patients presented with acute onset neurologic deficits within 1-4 days after administration of ACS regimen, with ICH scores of 3-4 signifying a high mortality rate of 72-90%. 6 out 7 patients had significant volume of ICH with mass effects, and 1 with subarachnoid hemorrhage. This lead to poor outcome in all patients with 6 out of 7 mortalities and 1 left with substantial disability. It was found that given the total number of patients administered with the said treatment, there is a low incidence of ICH.

Study on Post-marketing Drug Risk Management Plan in Japan and Its Enlightenment to China / 中国药房

OBJECTIVE：To provide reference for i mproving the post-marketing drug risk management in China by refering to the experience of post-marketing drug risk management plan （RMP）in Japan. METHODS ：The process of post-marketing drug regulation in Japan was introduced ，and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use （ICH）guidelines embodied in RMP in Japan were analyzed. The formulation and application of RMP in Japan during the post-marketing safety management were studied. And suggestions were offered for the improvement of post-marketing drug risk management in China. RESULTS & CONCLUSIONS ：The post-marketing regulation of drugs in Japan is characterized with dynamic regulation and social co-governance. ICH principle runs through the RMP management in Japan. Safety specification and risk minimization activities stipulated in RMP in Japan are consistent with ICH guidelines. RMP is defined in Pharmaceutical Affairs Law in Japan ，and is formulated and implemented under the guidance of the Good Vigilance Practice ；the changes are made under the guidance of the Good Post-marketing Study Practice. RMP is a necessary document for the registration and the re-review of new drugs in Japan ，its formulation is responsible by pharmaceutical enterprise ；RMP of new drug is available to the public through the subscription media system of Pharmaceuticals and Medical Devices Agency （PMDA）， which reflects the multi-governance of the government-pharmaceutical enterprises-the public. In China ，RMP supervision is not systematic and is inexperienced，and there is a lack of guidance documents and insufficient application of information and communication technology. It is suggested that China should strengthen post-marketing safety data management ，promote the connection between sentinel hospitals and pharmacovigilance systems of pharmaceutical enterprise ，increase the application of information and communication technology. Relevant normative documents and guidance documents of RMP should be issued by National Medical Products Administration. And the post-marketing supervision system for drugs should be clarified. Taking RMP publicity as an opportunity promote drug risk mamagement co-government ， realize sunshine and scientific supervision .

Enlightenment of international pharmacovigilance system on establishment of pharmacovigilance system of Chinese medicine / 中国中药杂志

Pharmacovigilance system is an extension of the original adverse drug reactions monitoring and reporting system as well as an internationally recognized basic system that must be matched with the whole life cycle supervision of drugs. European Union(EU)pharmacovigilance system, World Health Orgnization(WHO) Uppsala Monitoring Center system and ICH system are internationally recognized pharmacovigilance systems. They all have their own pharmacovigilance characteristics and could provide guarantee for clinical safe drug use. With the deepening of international communication, pharmacovigilance has also been developed in China. Pharmacovigilance of Chinese medicine is a new concept based on the existing pharmacovigilance system of chemical medicine and the characteristics of Chinese medicine. In ancient China, Chinese medicine also had its own ways of early warning. Ancient medical books have records on the toxicity classification, clinical pharmacovigilance and intoxication rescue of Chinese medicine. With the increase of public recognition of Chinese medicine in recent years, especially since the government issued the 13 th Five-Year Plan for the development of Chinese medicine, the pharmaceutical industry in China has paid more and more attention to the pharmacovigilance of Chinese medicine.However, the pharmacovigilance system of Chinese medicine has not yet been established, and it still needs to be explored and improved.Therefore, it is very necessary to develop the system to standardize pharmacovigilance-related activities of Chinese medicine. In this context, this study analyzed and learned the characteristics of pharmacovigilance systems of EU, ICH, and WHO Uppsala Monitoring Center, so as to provide some enlightenment for the establishment and improvement of pharmacovigilance system of Chinese medicine.

Rp-Hplc Method Development And Validation For The Combination Of Imiquimod And Salicylic Acid

Objective: The present study was undertaken to develop and validate an RP-HPLC method for the combination of imiquimod and salicylic acid Methods: The method was carried out on Nucleodur C18 (250 mm × 4.6 mm I.D., 5 ????m) using low-pressure gradient elution mode. The mobile phase was used as 30M potassium dihydrogen phosphate and acetonitrile (45:55) pH 6.5 adjusted using ortho-phosphoric acid. The concentration of solvents was 1-20 µg/ml and the volume of injection was 20 mcl with the flow rate of 1.0 ml/min. The absorption maxima of salicylic acid and imiquimod were found 234 nm and 226 nm, respectively. Results: The method was validated and showed the linearity greater than 0.99% and with precision (RSD%<1). The limit of detection (LOD) and limit of quantification (LOQ) of salicylic acid was found to be 0.09756 µg/ml and 0.2956 µg/ml, respectively, and imiquimod was found to be 0.044031 µg/ml and 0.13334 µg/ml, respectively. Conclusion: The method developed in the present study was found to be sensitive, specific, and can be applied for the simultaneous estimation of imiquimod and salicylic acid.

Simultaneous detection and quantification of bronchodilators in pure form and from in-vitro drug release of a novel combinational formulation

The analytical method was developed and validated for the quantification of salbutamol sulfate (SS) and ipratropiumbromide (IPB) in accordance with the International Council for Harmonization guidelines in its pure form. Thechromatographic partition was completed utilizing a blend of acetonitrile:phosphate buffer (30:70 v/v) with the pHscale adjusted to 3.0 using o-phosphoric acid at a flow rate of 1 ml/minute in Luna C-18(2)(150 × 4.6 mm i.d., 5 μm)column. The wavelength for detection was fixed at 212 nm. The SS and IPB showed a standard linearity curve in therange of 2–12 µg/ml, with retention time at 2.4 and 3.8 minutes, respectively. The developed method was reported tobe specific, linear (r2 ≥ 0.999), precise at intraday and interday levels (% relative standard deviation < 2.0%), accurate(% recovery: 96.02%–103.62%), and robust. The limit of detection and limit of quantification for SS was found to be0.42 and 1.26 µg/ml, while that of IPB was 0.44 and 1.34 µg/ml, respectively. Additionally, the developed method waseffectively applied in quantifying SS and IPB from its pure, commercial, and in-house prepared transdermal system tounderstanding the in-vitro drug release pattern from patches.

LC-MS method development for the quantitation of potential genotoxic impurity 2-Methyl-6-nitro aniline in Telmisartan API

Current work discloses the sensitive LC-MS/MS method development for the trace level determination of genotoxicimpurity 2-Methyl-6-nitro aniline in Telmisartan. 2-Methyl-6-nitro aniline was determined by LC-MS/MS methodin selected ion monitoring mode using LiChrospher RP-18 (100 × 4.6 mm) 5.0 µm column. Gradient technique wasapplied for the elution of analytes using acetonitrile (mobile phase A) and 0.01 M ammonium acetate buffer (mobilephase B) in different ratios. The gradient program (T/%B) was set as 0/5, 2.50/15, 5.00/30, 10.00/50, 15.00/95, and20.00/95. Developed method was validated as per International Conference on Harmonization guidelines. The limit ofdetection and limit of quantitation values found for 2-Methyl-6-nitro aniline were 0.05 and 0.1 µg/ml. The developedmethod serves as an upright tool in quality control for quantitation of 2-Methyl-6-nitro aniline impurity at trace levelsin Telmisartan.

ICH Score and Basal Plasma D-Dimer in Patients with Intracerebral Haemorrhage

Intracerebral haemorrhage constitutes 10-20 % of all strokes & remains without treatment of proven benefit & has higher risk of morbidity & mortality than cerebral infarction or subarachnoid bleed. Thus, these models may accurately predict outcome, and hence the purpose of this study is to define a clinical grading scale for patients with ICH which uses criteria that are predictive of outcome & that can be rapidly & accurately assessed at the time of presentation in emergency/casualty. Estimation of basal plasma D-dimer levels an indicator of systemic activation of coagulative & fibrinolytic system has shown to a powerful predictor of both early neurological worsening & mortality outcome & hence the present study is undertaken.METHODSThe study was carried out in the IPD of Department of General Medicine, Basaveshwara Teaching and General Hospital, Kalaburagi, attached to Mahadevappa Rampure Medical College. It is a cross sectional study conducted among 100 intracerebral bleed patients between November 2018 to November 2019 with simple random sampling procedure. Patients were followed up at the end of 1 month with telephone/letter/email.RESULTSThe mortality among patients who scored 0 of ICH scale was 0%, ICH score of 1 was 13.6 %, ICH score of 5 was 100 %. No patient scored 6. Higher the ICH score, higher is the mortality. Mortality among patients with D-Dimer value between 1500 – 5000 ng/ml is 55.2 %, and > 5000 ng/ml is 92.3 %. Above table indicates that higher the basal level of D-Dimer value higher is the mortality. Mortality among patients of either sex was equal i.e., 50 % between 8 - 15 days, and no deaths were noted between 15 - 30 days.CONCLUSIONSIntracerebral haemorrhage (ICH) has remained a serious disease despite recent improvements in management. So, efforts must be directed towards better understanding and modification of risk factors. The major risk factor in our study was hypertension. The other common risk factors were alcohol consumption and smoking. Thus, measures to ensure adequate control of hypertension/compliance of treatment among hypertensive, abstinence from alcohol and smoking may reduce the incidence of ICH. High initial plasma D-Dimer levels would indicate bad prognosis in ICH. In addition to diagnosis of ICH, CT Scan can also be used as a useful tool in assessing prognostic outcome of ICH, by using radiological parameters like larger volume of haematoma, presence of midline shift, intraventricular extension of haemorrhage and hydrocephalus which indicated bad prognosis i.e., using ICH score, higher the ICH score higher is the mortality.

A Novel Spectrophotometric and RP-HPLC methods for Determination of Nortriptyline hydrochloride and Pregabalin in Tablets

A Simple, rapid, specific, accurate, economical and precise UV spectrophotometric and RP-HPLC methods (inaccordance with ICH guidelines) were developed and validated for determination of Nortriptyline hydrochlorideand Pregabalin in tablet dosage form. The first method was based on Q - absorbance ratio, and absorbances ofboth drugs were determined at 239 nm (λmax of Nortriptyline Hydrochloride) and 235 nm (Iso-absorptive Point)when dissolved in methanol. It is found that Pregabalin does not have chromophoric group. To be UV-sensitive,it was compulsory to introduce chromophoric group in Pregabalin structure and make it UV-sensitive. This wasachieved by converting the primary amine group of Pregabalin through reaction with benzoyl chloride to formbenzoylated derivative of Pregabalin. Benzoylated Pregabalin was determined at 225 nm using UV-visiblespectrophotometer. The second method was based on RP-HPLC. The chromatographic separation was performedon an Inertsil ODS C18 column (250 x 4.6mmx 5 μm) with a mobile phase of 0.56 %w/v Sodium hexane sulphonicacid dissolved in water acetonitrile (50:50 %v/v, pH 4.5 adjusted with Glacial Acetic Acid) at flow rate of 1.0mL/min with DAD detection wavelength at 210 nm. Retention times of Nortriptyline Hydrochloride andPregabalin were 7.3894 min and 4.0506 min, respectively. Beer-Lambert’s law obeyed the concentration rangeof 2-12 μg/mL for Nortriptyline Hydrochloride and 10-60 μg/mL for Pregabalin. The results indicated that bothspectrophotometric and RP-HPLC methods were linear, accurate, precise and robust with RSD values less than0.2% and % recovery was within the standard limits (99 - 102%).

Stability indicating RP-HPLC method for simultaneous determination of pyrimethamine and sulfamethoxypyrazine in pharmaceutical formulation: Application to method validation

The present work takes into account the development of Reverse Phase High Performance Liquid Chromatography(HPLC) for simultaneous method estimation and validation of pyrimethamine and sulfamethoxypyrazine inpharmaceutical formulation. The chromatographic separation was accomplished on C8 column by using acetonitrileand potassium dihydrogen phosphate as the mobile phase (60:40 v/v) having a flow rate of 0.8 ml/minute. Theeluent was detected at 254 nm, simultaneously for both the drugs. The retention time for pyrimethamine andsulfamethoxypyrazine was found to be 3.33 and 4.21 minutes, respectively. According to the International Conferenceon Harmonisation guidelines, the develop method was validated in terms of accuracy, precision, linearity, limit ofdetection, limit of quantitation, robustness, and stress degradation studies. This validated method can be suggested forthe routine simultaneous laboratory analysis of pyrimethamine and sulfamethoxypyrazine.

Related Impurities High-Performance Liquid Chromatography Method Development And Validation For Drug Combinations: Olmesartan Medoxomil, Chlorthalidone And Cilnidipine

The liquid chromatography mass spectrometry (LC-MS) compatible, stability-indicating, specific, linear, accurate, sensitive with less run-time related impurities reversed phase high-performance liquid chromatography (RP-HPLC) related impurities method has been developed for olmesartan medoxomil (OLM), chlorthalidone (CHLR), and cilnidipine (CIL) drug combinations, and the method has been validated according to ICH and US-FDA guidelines. The chromatographic separation was performed by using Hypersil-BDS Thermo-Scientific, C18 (12.5 cm, 4.6 mm, 5 microns particle size) column. Mobile phase-A was prepared by mixing 3.85 gm ammonium acetate in HPLC water and adjust pH 5.0 by using diluted acetic acid. Acetonitrile was taken as mobile phase-B. Initial mobile phase ratio (55:45 v/v) was adjusted for mobile phase-A: mobile phase-B followed by gradient program. Other chromatographic conditions such as column temperature 25 degrees, flow rate 1.0 mL/minutes with the detection wavelength at 260 nm. The retention time for CHLR impurity A, olmesartan (OL), OLM impurity A, were found about 2.7, 3.3, and 7.2 minutes respectively, with a total run time of 18.0 minutes. The linearity calibration plot was performed and found linear relationship over the concentration range of 1.25 limit of quantitation (LoQ)–18.75 μg/mL, 3.6 LoQ–60.0 μg/mL, 3.6 LoQ– 60.0 μg/mL respectively for CHLR impurity A, OL and OLM impurity A respectively. The limit of detection (LoD) and LoQ were found 0.4 ppm (μg/mL) and 1.2 ppm (μg/mL), 1.2 ppm (μg/mL) and 3.5 ppm (μg/mL), 1.1 ppm (μg/mL) and 3.3 ppm (μg/mL) for CHLR impurity A, OL and OLM impurity A respectively. The accuracy was determined by recovery studies and was found between 90.0–110.0%. The developed analytical method has been validated for LoD-LoQ, specificity, linearity, accuracy, precision, robustness, and ruggedness, which were well within the acceptance limit as per ICH guidelines. All the degradation products generated by stress conditions were found to be well separated from one another (all drug components and impurities). The developed method with shorter runtime was successfully implemented for routine quality control and stability analysis to check the quality of OLM, CHLR, and CIL drug combinations.

A novel analytical liquid chromatography–tandem mass spectrometry method for the estimation of Ribavirin in bulk and pharmaceutical formulation

The aim of this study is to develop and validate a method that is simple, precise, sensitive, and rapid compared tousing the liquid chromatography–tandem mass spectrometry method for the quantitative determination of Ribavirin(antiviral drug) in its tablet formulation. The development and validation of the method were achieved using a column(Zorbax 50 mm × 4.6 mm × 5 µm) with mobile phase ammonium formate (pH: 7.50): acetonitrile in the ratio (30:70,v/v) with the flow rate of 0.5 ml/min. The retention time for Ribavirin was 1.1 minutes with the total run time of2.5 minutes. The linearity range for Ribavirin was from 2 to 100 ng/ml with a correlation coefficient of 0.9956. Thedetection and quantitation limits of Ribavirin are 0.7 and 2 ng/ml, respectively. The percentage recovery of Ribavirinranged from 94.00% to 98.33%. The percentage relative standard deviation for intraday and interday precision resultswas found to be 0.67%–2.11% and 1.92%–3.11%, respectively. The new method developed for Ribavirin drug wasfound to be rapid, sensitive, selective, and economical. The established method was the evaluation of Ribavirin in itsmarketed formulation (tablet). The values obtained from the analysis were found out to be within the acceptable limitsas per the International Council for Harmonisation (ICH) guidelines.

Effect of acupuncture on NLRP3 inflammatory corpuscle in rats with intracerebral hemorrhage / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture at "Baihui" (GV 20) through "Qubin" (GB 7) on NLRP3 inflammatory corpuscle in rats with intracerebral hemorrhage (ICH), and to explore the action mechanism of acupuncture on promoting the recovery of neural function in rats with ICH.@*METHODS@#Forty SPF six-week-old male SD rats were randomly divided into a sham operation group, a model group, a non-acupoint group and an acupuncture group, 10 rats in each group. The rats in the model group, non-acupoint group and acupuncture group were intervened with autologous blood injection to prepare ICH model, while the rats in the sham operation group were only intervened with operation but not injection with autologous blood. About 3 hours after the establishment of the model, the rats in the acupuncture group were intervened with acupuncture at "Baihui" (GV 20) through "Qubin" (GB 7), once every 12 hours, for 7 days; the rats in the non-acupoint group were intervened with acupuncture at the non-acupoint [parallel to the "Baihui" (GV 20), 1 cm next to the midline] on the affected side, and other treatment was the same as the acupuncture group. At the end of the intervention, the composite nerve function score of each group was evaluated; the histomorphology of the hemorrhage penumbra was observed by HE staining; the expression of NLRP3 inflammatory corpuscle in the brain was detected by immunohistochemistry; the relative protein expression levels of NLRP3, interleukin-1β (IL-1β) and interleukin-18 (IL-18) in brain were detected by the method of Western blot.@*RESULTS@#Seven days into intervention, compared with the sham operation group, each item score and total score of composite nerve function in the model group were significantly reduced (<0.01, <0.05). There was edema and karyopyknosis in brain neuron as well as necrocytosis and inflammatory cell infiltration in the model group. Compared with the model group and the non-acupoint group, the total score of composite nerve function and the scores of symmetrical movement of limbs (LS) and proprioception of tentacles (VP) in the acupuncture group were increased (<0.01, <0.05), and the cell necrosis and inflammatory cell infiltration were relieved. Compared with the sham operation group, NLRP3 inflammatory corpuscle expression and the relative protein expression levels of NLRP3, IL-1β and IL-18 in brain tissue in the model group were increased (<0.01); compared with the model group and the non-acupoint group, NLRP3 inflammatory corpuscle expression and the relative protein expression levels of NLRP3, IL-1β and IL-18 in brain tissue in the acupuncture group were reduced (<0.01).@*CONCLUSION@#Acupuncture at "Baihui" (GV 20) through "Qubin" (GB 7) could downregulate the expression of NLRP3, IL-1β and IL-18 in the brain tissue of ICH rats, inhibit the inflammatory response, and promote the recovery of neural function.

A extimidade do supereu e um sujeito melancolizado / The extimity of the Superego and a melancholized subject / L'extimité du surmoi et un sujet mélancolisé / La extimidad del superyó y un sujeto melancolizado

Na história da psicanálise, o conceito de supereu é objeto de inúmeros estudos por introduzir questões teóricas que exigem precisões sempre maiores. Uma delas diz respeito à articulação com alguns aspectos do conceito de Outro, em Lacan. Pretendemos contribuir ao debate, com a clínica da melancolia, seguindo à risca as orientações de Freud, inclusive em nossa leitura de Lacan, para o que nos servimos também de alguns outros autores. Chamamos a atenção para a tradução do verbo eintauchen, com o qual Freud identifica o mecanismo que relaciona o supereu com o isso. Um caso clínico ilustra de que modo o supereu imerge no isso para então, servindo-nos dos desenvolvimentos topológicos de Lacan, verificarmos de que maneira o toro do Outro pode imergir no interior do envelope das demandas, imergindo no isso, como dizia Freud, reservatório da pulsão que é, fundamentalmente, pulsão de morte.

In the history of psychoanalysis, the concept of superego is the object of countless studies for introducing theoretical questions that require increasingly greater precisions. One of them concerns the articulation with some aspects of the concept of the Other in Lacan. We intend to contribute to the debate, with the clinic of melancholy, following the guidelines of Freud, even in our reading of Lacan, to which we also make use of some contributions from other authors. We call the attention to the translation of the verb eintauchen, with which Freud identifies the mechanism that relates the superego to the it (id). A clinical case illustrates how the superego immerses in the it, and then, using the topological developments of Lacan, we try to see how the torus of the Other can immerse itself within the envelope of demands, immersing in the it, as Freud used to say, the reservoir of the drive that is fundamentally the death drive.

Dans l'histoire de la psychanalyse, le concept du surmoi fait l'objet d'innombrables études car il introduit des questions théoriques nécessitant des précisions toujours plus grandes. L'une d'elles concerne l'articulation avec certains aspects du concept de l'Autre de la théorie de Lacan. Nous essayons de contribuer au débat, à la clinique de la mélancolie, en suivant rigoureusement les directives de Freud, y compris dans notre lecture de Lacan, et également d'autres auteurs. Nous attirons l'attention sur la traduction du verbe « eintauchen ¼, par lequel Freud identifie le mécanisme reliant le surmoi et la « chose ¼. Un cas clinique illustre la manière dont le surmoi s'immerge dans la chose. En utilisant les développements topologiques de Lacan, nous vérifions comment le tore de l'Autre peut s'immerger dans l'enveloppe des demandes en s'immergeant, comme disait Freud, dans le réservoir de la pulsion qui est, fondamentalement, pulsion de mort.

En la historia del psicoanálisis, el concepto del superyó ha sido objeto de innumerables estudios, ya que introduce cuestiones teóricas que siempre requieren mayores precisiones. Una de ellas se refiere a la articulación con algunos aspectos del concepto de Otro, en Lacan. Se pretende contribuir al debate con la clínica de la melancolía, siguiendo al pie de la letra las orientaciones de Freud, incluso en nuestra lectura de Lacan, para lo cual también consultamos a otros autores. Llamamos la atención sobre la traducción del verbo eintauchen, con el que Freud identifica el mecanismo que relaciona al superyó con el ello. Un caso clínico ilustra de qué manera el superyó se sumerge en el ello para entonces, sirviéndonos de los desarrollos topológicos de Lacan, verificar de qué manera el toro del Otro puede sumergirse en el interior del sobre de las demandas, sumergiéndose en el ello, como decía Freud, reservorio de la pulsión que es fundamentalmente pulsión de muerte.

In der Geschichte der Psychoanalyse ist das Konzept des Über-Ichs bis heute Gegenstand zahlloser Studien, da es theoretische Fragen aufwirft, die zunehmend präzisere Antworten erfordern. Eine dieser Fragen betrifft den Zusammenhang mit einigen Aspekten des Konzepts des Anderen von Lacan. Dieser Artikel untersucht die Klinik der Melancholie gemäß Freuds Richtlinien, sogar in unserer Lektüre von Lacan, zu der wir auch einige Beiträge anderer Autoren zu Hilfe nehmen. Wir weisen auf die Übersetzung des Verbes eintauchen hin, mit dem Freud den Mechanismus identifiziert, der das Über-Ich mit dem Es in Beziehung setzt. Anhand eines klinischen Falles zeigen wir auf, wie das Über-Ich in das Es eintaucht und untersuchen dann - anhand der topologischen Entwicklungen von Lacan - wie der Torus des Anderen in die Hülle der Forderungen eintauchen kann, eintauchend, wie Freud sagte, in das Reservoir des Triebes, der im Grunde der Todesantrieb ist.

A Rapid Validated Uni-Dimensional Double Development Hptlc-Densitometry Method For Simultaneous Estimation Of Metformin Hydrochloride, Gliclazide And Pioglitazone Hydrochloride

Objective: To develop and validate a uni-dimensional double development high-performance thin layer chromatography (UDDD-HPTLC) for estimation of anti-diabetic medicine compromising of metformin (MET) gliclazide (GLZ) and pioglitazone hydrochloride (PIO). Methods: The chromatographic separation of these drugs was carried out on precoated TLC plates silica gel 60F254by two mobile phases consisting of Ammonium Sulphate: Methanol: Acetonitrile: Water (4:3:2:1) for MET and PIO and Toluene: Ethyl Acetate: Formic Acid (6:4:0.5) for GLZ respectively for ideal separation and good resolution. The densitometric detection and quantification were carried out at 237 nm for MET and 200 nm for GLZ and PIO. The validation parameters were strictly followed as per the ICH guidelines. Results: The linearity range was obtained at 3000-8000ng/spot, 360-960 ng/spot, 90-240 ng/spot for MET, GLZ and PIO with r2value>0.999. The other parameters such as precision, reproducibility, robustness were efficiently obtained within the limits. The proposed method was successfully applied for simultaneous determination of MET, GLZ and PIO in the commercial formulation. Conclusion: In simultaneous estimation, the different polarity of drugs makes it more cumbersome to develop and validate any chromatographic method. In the present study, a uni-dimensional double development high-performance thin layer chromatography (UDDD-HPTLC) for estimation of these drugs have been developed and validated to resolve the estimation problem. It is an effortless and speedy method which was developed and validated using ICH guidelines. The developed and validated method using ICH guidelines is effortless and speedy technique.

Novel Hptlc-Densitometric Method For The Estimation Of Teriflunomide In Tablet Dosage Form

Objective: The current work is intended towards the development of a novel, simple and precise high-performance thin layer chromatographic (HPTLC) method coupled with a densitometer for the estimation of teriflunomide (TEF) present in the marketed formulation. Methods: The chromatographic development was performed on aluminum plates coated with silica gel 60 F254 using toluene: ethyl acetate: glacial acetic acid (7.5:2: 0.5 v/v/v) as the mobile phase. Densitometric scanning was achieved at the absorbance maxima, UV 284 nm. Results: Well separated band was observed with Rf value 0.46. The calibration curve plotted in the concentration range 100-700ng/band exhibited an excellent linear relationship with the r2 value of 0.9928. The method was found to comply with all the validation parameters as per the ICH guidelines. Conclusion: The method ensures minimal use of mobile phase with minimal run time compared to other reported analytical methods. This validated method can be used by quality control laboratories for the routine quantitative analysis of tablets consisting of Teriflunomide.

Method Development And Validation Of Donepezil Hydrochloride By Using Uv Spectrophotometric Method

Abstract: Simple, specific, accurate and cost economic UV spectrophotometric methods weredeveloped and validated for determination of Donepezil Hydrochloride. Instead of usingorganic solvents, mixture of Acetonitrile and water was used during method development andvalidation. Donepezil hydrochloride standard solution was scanned in the UV range (400-200nm) in a 1cm quartz cell in a double beam UV spectrophotometer. The standard solution ofDonepezil Hydrochloride showed maximum absorption at wavelength 231 nm. The methodobeys Beer’s law in the concentration range from 4-20µg/ml. The correlation coefficient wasfound to be 0.9983and regression of the curve was found Y=0.0376x+0.0185 with excellentrecovery 99.66-100.83%. Limit of detection and limit of quantification were found to be0.197µg/ml and 0.6µg/ml respectively. The ruggedness and robustness were performed. Themethod was validated for several parameters like accuracy, precision as per ICH guidelines.Statistical analysis proved that the methods are repeatable and specific for determination ofthe drug. These methods can be adopted in the routine assay analysis of DonepezilHydrochloride in API and pharmaceutical dosage form.