Hypertonic environment regulates cadherin expression and affects em-bryoid body differentiation / 中国病理生理杂志

AIM:Given the uncertain impact of osmotic pressure on embryoid body(EB)differentiation,this study aimed to investigate the effects of increased osmotic pressure on EB differentiation and explore the potential relation-ship between this process and cadherin.METHODS:Polhethylene glycol 300(PEG 300)was used to increase the os-motic pressure of the culture medium used for cultivating EBs under both high osmotic pressure and standard culture condi-tions.The experimental design included a control group,an experimental group(hypertonic group),groups treated with varying concentrations of PEG 300,and an experimental group treated with an inhibitor.Western blot,RT-qPCR,AM/PI staining,CCK-8,and immunocytochemical staining was used to analyze the cell viability and the expression of CDH1 and CDH2 markers of the three germ layers,and pluripotency markers within the EBs.RESULTS:Hypertonicity did not af-fect cell viability.Significant differences were observed in the expression of the cadherin proteins CDH1 and CDH2 in EBs between the experimental and control groups;however,no cleartrend towards an EMT shift was observed.Specifically,CDH2 expression was significantly down-regulated in experimental group,showing a clear correlation with variations in os-motic pressure.Moreover,compared with control group,pluripotency markers in the EBs from experimental group exhibited significantly higher expression levels from the 2nd day to the 5th day.A substantial increase in the expression of mesoder-mal markers was also observed;however,a downward trend was observed for ectodermal markers in experimental group.Intervention using SB431542,which up-regulates CDH2 expression by affecting TGF-β signaling,reversed the expression trend of mesodermal and ectodermal markers in experimental group.CONCLUSION:Elevated osmotic pressure appears to enhance the mesodermal differentiation efficiency in EBs,possibly correlating with CDH1 and CDH2 changes induced by osmotic pressure.Therefore,this study emphasizes the significant role of osmotic pressure in stem cell applications.

A survey on osmotic fragility of erythrocytes in plateau population / 中国输血杂志

【Objective】 To study the changes in erythrocyte osmotic fragility(EOF) in patients with hypercythemia, polycythemia and anemia under a high altitude environment. 【Methods】 A total of 174 outpatients, inpatients and people undergoing physical examination in Tibet Autonomous Region People′s Hospital in October 2020 were enrolled and divided into four groups according to hemoglobin levels: the polycythemia group(n=42), the physiologic increase group(n=48), the anemia group(n=29) and the healthy control group(n=55). They were compared with 67 anemia patients and 67 healthy people in the laboratory of Peking Union Medical College Hospital in the same period as the plain control group. The classic EOF test method was used to compare the results of each group′s EOF. The concentrations of NaCl solution for starting hemolysis (STH) and NaCl solution for complete hemolysis (CTH) were included, and the data were statistically analyzed by SPSS software. 【Results】 There was a significant difference in CTH between Zang and Han healthy people (P<0.05). STH in high altitude polycythemia group(0.52) was higher than that in high altitude healthy control group(0.48) (P<0.001). Compared with plain, the median CTH of plateau anemia group(0.36) and plateau health control group(0.36) was significantly higher than that of plain anemia group(0.28) and plain control group(0.28) (P<0.001). Multivariate logistic regression analysis showed that plateau region, female polycythemia and anemia were risk factors for STH elevation. 【Conclusion】 This study finds that the EOF increases in the plateau population and patients with polycythemia, which provides reference for studying red blood cell disorders and blood transfusion strategy in the plateau region.

Experience of Rehabilitation Treatment for Osmotic Demyelination Syndrome with Locked-in Syndrome / The Japanese Journal of Rehabilitation Medicine

Osmotic demyelination syndrome is a pathological condition that leads to electrolyte imbalances and rapid correction, resulting in pseudobulbar palsy, quadriplegia, and altered consciousness. Approximately 33-55％ of affected patients experience residual functional impairment. Herein, we describe a case of a patient with osmotic demyelination syndrome who developed locked-in syndrome during the disease course, underwent rehabilitation treatment, and achieved complete remission without sequelae.The patient was a 47-year-old man who was admitted to hospital A owing to weakness in the lower extremities and dysarthria. He had severe hyponatremia and received sodium correction. However, on hospital day 9, dysarthria redeveloped and involuntary finger movements were noted. Osmotic demyelination syndrome was suspected based on the findings of magnetic resonance imaging of the head and clinical course, leading to his transfer to hospital B. Steroid pulse and rehabilitation therapies were initiated at hospital B. By the 19th day of symptom onset, his limb and facial muscle paralysis progressed, leading to locked-in syndrome. Thereafter, the patient was transferred to hospital C, where he received physiotherapy, occupational therapy, and eating training, markedly improving his physical functions. He was discharged from hospital C, 4 months after the symptom onset, with limited range of motion of the fingers and weakness of the extremities and continued to receive outpatient rehabilitation treatment. His symptoms improved further, and 1 year after the onset of symptoms, he returned to work without any sequelae.

Oxidative and osmotolerant effects in Salvator merianae (Squamata: Teiidae) red blood cells during hibernation

Abstract Hibernation is a natural condition of animals that lives in the temperate zone, although some tropical lizards also experience hibernation annually, such as the lizard native from South America, Salvator merianae, or tegu lizard. Even though physiological and metabolic characteristic associated with hibernation have been extensively studied, possible alterations in the red blood cells (RBC) integrity during this period remains unclear. Dehydration and fasting are natural consequences of hibernating for several months and it could be related to some cellular modifications. In this study, we investigated if the osmotic tolerance of RBCs of tegu lizard under hibernation is different from the cells obtained from animals while normal activity. Additionally, we indirectly investigated if the RBCs membrane of hibernating tegus could be associated with oxidation by quantifying oxidized biomolecules and the activity of antioxidant enzymes. Our findings suggest that RBCs are more fragile during the hibernation period, although we did not find evidence of an oxidative stress scenario associated with the accentuated fragility. Even though we did not exclude the possibility of oxidative damage during hibernation, we suggested that an increased RBCs volume as a consequence of hypoosmotic blood during hibernation could also affect RBCs integrity as noted.

Resumo A hibernação é uma condição natural dos animais que vivem na zona temperada, embora alguns lagartos tropicais também experenciem hibernação anualmente, como é o caso do lagarto nativo da América do Sul, Salvator merianae ou teiú. Embora as características fisiológicas e metabólicas associadas à hibernação tenham sido amplamente estudadas, possíveis alterações na integridade das hemácias durante esse período ainda permanecem obscuras. A desidratação e o jejum são consequências naturais da hibernação por vários meses e podem estar relacionadas a algumas modificações celulares. Neste estudo, investigamos se a tolerância osmótica de hemácias do lagarto teiú sob hibernação são diferentes das células obtidas de animais em atividade normal. Além disso, investigamos indiretamente por meio da quantificação de biomoléculas oxidadas e da atividade de enzimas antioxidantes se a membrana das hemácias dos teiús em hibernação poderia estar associada à oxidação. Nossos resultados sugerem que as hemácias possuem maior fragilidade durante o período de hibernação, embora não tenhamos encontrado evidências de um cenário de estresse oxidativo associado à essa fragilidade acentuada. Embora não tenhamos excluído a possibilidade de dano oxidativo durante a hibernação, sugerimos que um aumento no volume das hemácias como consequência de sangue hipoosmótico durante a hibernação também poderia afetar a integridade de hemácias, tal como foi observado.

Photosynthetic acclamatory response of Panicum antidotale Retz. populations to root zone desiccation stress

Abstract Growth of plants is severely reduced due to water stress by affecting photosynthesis including photosystem II (PSII) activity and electron transport. This study emphasised on comparative and priority targeted changes in PSII activity due to progressive drought in seven populations of Panicum antidotale (P. antidotale) collected from Cholistan Desert and non-Cholistan regions. Tillers of equal growth of seven populations of P. antidotale grown in plastic pots filled with soil were subjected progressive drought by withholding water irrigation for three weeks. Progressive drought reduced the soil moisture content, leaf relative water content, photosynthetic pigments and fresh and dry biomass of shoots in all seven populations. Populations from Dingarh Fort, Dingarh Grassland and Haiderwali had higher growth than those of other populations. Cholistani populations especially in Dingarh Grassland and Haiderwali had greater ability of osmotic adjustment as reflected by osmotic potential and greater accumulation of total soluble proteins. Maximum H2O2 under water stress was observed in populations from Muzaffargarh and Khanewal but these were intermediate in MDA content. Under water stress, populations from Muzaffargarh and Dingarh Fort had greater K+ accumulation in their leaves. During progressive drought, non-Cholistani populations showed complete leaf rolling after 23 days of drought, and these populations could not withstand with more water stress condition while Cholistani populations tolerated more water stress condition for 31 days. Moreover, progressive drought caused PSII damages after 19 days and it became severe after 23 days in non-Cholistani populations of P. antidotale than in Cholistani populations.

Resumo O crescimento das plantas é severamente reduzido devido ao estresse hídrico, afetando a fotossíntese, incluindo a atividade do fotossistema II (PSII) e o transporte de elétrons. Este estudo enfatizou as mudanças comparativas e prioritárias na atividade do PSII devido à seca progressiva em sete populações de Panicum antidotale (P. antidotale) coletadas no Deserto do Cholistão e regiões fora do Cholistão. Perfilhos de igual crescimento de sete populações de P. antidotale cultivadas em vasos de plástico cheios de solo foram submetidos à seca progressiva, retendo a irrigação com água por três semanas. A seca progressiva reduziu o teor de umidade do solo, teor de água relativo nas folhas, pigmentos fotossintéticos e biomassa fresca e seca dos brotos em todas as sete populações. Populações de Dingarh Fort, Dingarh Grassland e Haiderwali tiveram maior crescimento do que as de outras populações. As populações de Cholistani, especialmente em Dingarh Grassland e Haiderwali, apresentaram maior capacidade de ajuste osmótico, refletido pelo potencial osmótico e maior acúmulo de proteínas solúveis totais. H2O2 máximo sob estresse hídrico foi observado em populações de Muzaffargarh e Khanewal, mas estas foram intermediárias no conteúdo de MDA. Sob estresse hídrico, as populações de Muzaffargarh e Dingarh Fort tiveram maior acúmulo de K+ em suas folhas. Durante a seca progressiva, as populações não cholistanesas mostraram rolagem completa das folhas após 23 dias de seca, e essas populações não conseguiram suportar mais condições de estresse hídrico, enquanto as populações cholistani toleraram mais condições de estresse hídrico por 31 dias. Além disso, a seca progressiva causou danos ao PSII após 19 dias e tornou-se severa após 23 dias em populações não cholistanesas de P. antidotale do que em populações cholistanesas.

Photosynthetic acclamatory response of Panicum antidotale Retz. populations to root zone desiccation stress / Reação fotossintética aclamatória de Panicum antidotale Retz. populações submetidas ao estresse da dessecação da zona radicular

Abstract Growth of plants is severely reduced due to water stress by affecting photosynthesis including photosystem II (PSII) activity and electron transport. This study emphasised on comparative and priority targeted changes in PSII activity due to progressive drought in seven populations of Panicum antidotale (P. antidotale) collected from Cholistan Desert and non-Cholistan regions. Tillers of equal growth of seven populations of P. antidotale grown in plastic pots filled with soil were subjected progressive drought by withholding water irrigation for three weeks. Progressive drought reduced the soil moisture content, leaf relative water content, photosynthetic pigments and fresh and dry biomass of shoots in all seven populations. Populations from Dingarh Fort, Dingarh Grassland and Haiderwali had higher growth than those of other populations. Cholistani populations especially in Dingarh Grassland and Haiderwali had greater ability of osmotic adjustment as reflected by osmotic potential and greater accumulation of total soluble proteins. Maximum H2O2 under water stress was observed in populations from Muzaffargarh and Khanewal but these were intermediate in MDA content. Under water stress, populations from Muzaffargarh and Dingarh Fort had greater K+ accumulation in their leaves. During progressive drought, non-Cholistani populations showed complete leaf rolling after 23 days of drought, and these populations could not withstand with more water stress condition while Cholistani populations tolerated more water stress condition for 31 days. Moreover, progressive drought caused PSII damages after 19 days and it became severe after 23 days in non-Cholistani populations of P. antidotale than in Cholistani populations.

Resumo O crescimento das plantas é severamente reduzido devido ao estresse hídrico, afetando a fotossíntese, incluindo a atividade do fotossistema II (PSII) e o transporte de elétrons. Este estudo enfatizou as mudanças comparativas e prioritárias na atividade do PSII devido à seca progressiva em sete populações de Panicum antidotale (P. antidotale) coletadas no Deserto do Cholistão e regiões fora do Cholistão. Perfilhos de igual crescimento de sete populações de P. antidotale cultivadas em vasos de plástico cheios de solo foram submetidos à seca progressiva, retendo a irrigação com água por três semanas. A seca progressiva reduziu o teor de umidade do solo, teor de água relativo nas folhas, pigmentos fotossintéticos e biomassa fresca e seca dos brotos em todas as sete populações. Populações de Dingarh Fort, Dingarh Grassland e Haiderwali tiveram maior crescimento do que as de outras populações. As populações de Cholistani, especialmente em Dingarh Grassland e Haiderwali, apresentaram maior capacidade de ajuste osmótico, refletido pelo potencial osmótico e maior acúmulo de proteínas solúveis totais. H2O2 máximo sob estresse hídrico foi observado em populações de Muzaffargarh e Khanewal, mas estas foram intermediárias no conteúdo de MDA. Sob estresse hídrico, as populações de Muzaffargarh e Dingarh Fort tiveram maior acúmulo de K+ em suas folhas. Durante a seca progressiva, as populações não cholistanesas mostraram rolagem completa das folhas após 23 dias de seca, e essas populações não conseguiram suportar mais condições de estresse hídrico, enquanto as populações cholistani toleraram mais condições de estresse hídrico por 31 dias. Além disso, a seca progressiva causou danos ao PSII após 19 dias e tornou-se severa após 23 dias em populações não cholistanesas de P. antidotale do que em populações cholistanesas.

Oxidative and osmotolerant effects in Salvator merianae (Squamata: Teiidae) red blood cells during hibernation / Efeitos de oxidação e osmotolerância dos eritrócitos de Salvator merianae (Squamata: Teiidae) durante a hibernação

Abstract Hibernation is a natural condition of animals that lives in the temperate zone, although some tropical lizards also experience hibernation annually, such as the lizard native from South America, Salvator merianae, or "tegu" lizard. Even though physiological and metabolic characteristic associated with hibernation have been extensively studied, possible alterations in the red blood cells (RBC) integrity during this period remains unclear. Dehydration and fasting are natural consequences of hibernating for several months and it could be related to some cellular modifications. In this study, we investigated if the osmotic tolerance of RBCs of tegu lizard under hibernation is different from the cells obtained from animals while normal activity. Additionally, we indirectly investigated if the RBCs membrane of hibernating tegus could be associated with oxidation by quantifying oxidized biomolecules and the activity of antioxidant enzymes. Our findings suggest that RBCs are more fragile during the hibernation period, although we did not find evidence of an oxidative stress scenario associated with the accentuated fragility. Even though we did not exclude the possibility of oxidative damage during hibernation, we suggested that an increased RBCs volume as a consequence of hypoosmotic blood during hibernation could also affect RBCs integrity as noted.

Resumo A hibernação é uma condição natural dos animais que vivem na zona temperada, embora alguns lagartos tropicais também experenciem hibernação anualmente, como é o caso do lagarto nativo da América do Sul, Salvator merianae ou "teiú". Embora as características fisiológicas e metabólicas associadas à hibernação tenham sido amplamente estudadas, possíveis alterações na integridade das hemácias durante esse período ainda permanecem obscuras. A desidratação e o jejum são consequências naturais da hibernação por vários meses e podem estar relacionadas a algumas modificações celulares. Neste estudo, investigamos se a tolerância osmótica de hemácias do lagarto teiú sob hibernação são diferentes das células obtidas de animais em atividade normal. Além disso, investigamos indiretamente por meio da quantificação de biomoléculas oxidadas e da atividade de enzimas antioxidantes se a membrana das hemácias dos teiús em hibernação poderia estar associada à oxidação. Nossos resultados sugerem que as hemácias possuem maior fragilidade durante o período de hibernação, embora não tenhamos encontrado evidências de um cenário de estresse oxidativo associado à essa fragilidade acentuada. Embora não tenhamos excluído a possibilidade de dano oxidativo durante a hibernação, sugerimos que um aumento no volume das hemácias como consequência de sangue hipoosmótico durante a hibernação também poderia afetar a integridade de hemácias, tal como foi observado.

In vivo pharmacokinetics and in vitro-in vivo correlation of silymarin phospholipid complex microporous osmotic pump controlled-release tablets in beagle dogs / 药学实践与服务

Objective To evaluate the release characteristics in vitro, pharmacokinetics in rabbits and in vivo-in vitro correlation of silymarin phospholipid complex microporous osmotic pump controlled release tablets（SM-PC MPOP）. Methods The release characteristics of SM-PC MPOP in vitro were detected by HPLC in the artificial gastric fluid. Six beagle dogs were subjected to double cycle cross control, which were given SM-PC MPOP and Legalon（30 mg/kg）. The concentration of silybin in plasma was determined by HPLC and the data were processed by software. Results The cumulative release rate of SM-PC MPOP in vitro was over 85% in 12 h. The pharmacokinetics in beagle dogs showed that SM-PC MPOP and legalon conformed to double compartment first-order absorption model and the pharmacokinetic parameters were obtained: tmax:（3.2±0.4）and（0.9±0.1）h, Cmax:（0.298 6±0.068 9）and（0.629 9±0.076 5）μg/ml, AUC0→24:（2.996 8±0.583 3）and（2.268 9±0.432 8）h·μg /ml. The relative bioavailability of SM-PC MPOP was（162.21 ± 30.82）%. Conclusion SM-PC MPOP could release slowly, which could increase the relative bioavailability significantly. The correlation between the absorption in vivo and release in vitro was fine（r = 0.839 0）.

Development of a method for determination of osmotic pump controlled-release tablets of lorcaserin hydrochloride in beagle dog plasma and its application to pharmacokinetic study / 中国药理学通报

Aim To develop an UPLC-MS/MS method to determine the concentration of lorcaserin hydrochloride in beagle plasma, and study the pharmacokinetics of osmotic pump controlled-release tablets of lorcaserin hydrochloride. Methods A randomized crossover design was used, carbamazepine as the internal standard(IS), and plasma protein precipitation with acetonitrile. The chromatographic was Phenomenex Polar C18 column(100 mm×2. 1 mm, 3 μm), and acetonitrile - water(containing 10 mmol·L-1 ammonium acetate and 0.1% formic acid)(40:60, V/V)was mobile phase. Multiple reaction monitoring mode and electrospray positive ionization were used to detect lorcaserin hydrochloride. The MS/MS ion transitions were monitored at m/z 196.2→129.2 for lorcaserin hydrochloride and m/z 237→194.1 for carbamazepine, respectively. Results The linear range was 1 to 500 μg·L-1(r=0.999 2), the extraction recovery rate ranged from 87.70% to 89.70%, the precision RSD was 9.7%. The accuracy and matrix effect met the requirements, and the stability of lorcaserin hydrochloride was good in -20 ℃ refrigerator for 45 d, repeated freezing and thawing for three times, placed at room temperature for 24 h, and the disposed samples placed in automatsampler for 6 h were stable. The main pharmacokinetic parameters of the controlled-release tablet and immediate-release tablet were as follows:Tmax was(8.00±1.27)h and(1.00±0.13)h, Cmax was(70.56±3.73)μg·L-1 and(176.33±16.73)μg·L-1, and AUC0-t was(966.33±7.56)μg·h·L-1 and(973.05±69.09)μg·h·L-1, respectively. Conclusions The established UPLC-MS/MS method can be used to study the pharmacokinetics of lorcaserin hydrochloride in the plasma of beagle dogs, and osmotic pump controlled-release tablets has sustained release effect.

A case report of hereditary spherocytosis (HS): Approach to diagnosis and management of HS

Hereditary spherocytosis (HS) is a type of congenital hemolytic anemia, in which heterogeneous alterations in one of the six genes that encode for proteins involved in vertical associations which tie the red blood cell (RBC) membrane skeleton to the lipid bilayer causes dysfunction or deficiency of cell membrane protein resulting in spherical-shaped, hyper-dense, and poorly deformable RBCs with a shortened life span. We report a case of HS in a 2-month-old female who presented with severe anemia, jaundice, and hepatosplenomegaly. The peripheral blood smear showed spherocytosis and reticulocytosis. The osmotic fragility was positive and direct antiglobin test was negative. The osmotic fragility test and direct antiglobulin test were positive. She was managed with packed RBCs (PRBCs) transfusion and folic acid supplementation

Prevention and amelioration of erythrocyte instability observed under deficiency of vitamin B12 alone or combined with micronutrient limitation through dietary supplementation with Chlorella and Spirulina

Micronutrient rich microalgae, Chlorella and Spirulina, could be natural food supplements to overcome the micronutrient deficiency, increasingly recognised as a global health issue. In two independent experiments, the Spirulina and Chlorella were evaluated as prophylactic and ameliorative dietary supplements of vitamin B12. Erythrocyte stability (relative osmotic fragility and haemolysis percentage), haematological parameters, micronutrient deficiency (serum levels of iron, zinc), plasma vitamin B12 and vitamin B12 biomarker (methylmalonic acid) were analysed. The deficient groups receiving Spirulina and Chlorella as prophylactic dietary supplements showed a 1.34 to 1.41 folds increase in serum iron and a 2.13 to 2.19 folds increase in plasma vitamin B12, compared to B12 deficient group. Supplementation of Spirulina to ameliorate vitamin B12 deficiency combined with micronutrient limitation showed an increase of 1.14 folds and 1.2 folds in serum iron and zinc respectively and 1.51 folds in plasma vitamin B12 compared to the deficient group. The relative osmotic fragility of erythrocytes in deficient experimental animals was 17 to 45% higher compared to the control. The osmotic fragility and deformation in the morphology of erythrocytes observed under vitamin B12 deficiency, alone or in combination with micronutrient limitation, were prevented and ameliorated on dietary supplementation with the microalgal biomass.

Application of ultrasound monitoring optic nerve sheath diameter in diagnosis and treatment of adult patients with intracranial hypertension / 中国医师进修杂志

Objective:To investigate the effect of ultrasound measurement of optic nerve sheath diameter (ONSD) in adult patients with elevated intracranial pressure (ICP).Method:From June 2017 to March 2020, A total of 64 patients (32 patients with elevated ICP and 32 patients with normal ICP) were placed with invasive intracranial pressure monitoring probe in Beijing Pinggu Hospital. Their ICP and ONSD were continuously monitored. Thirty-two healthy volunteers were recruited as control group to check ONSD. The correlation between ONSD and ICP, and the changes of ICP and ONSD after osmotic therapy were observed.Results:The ONSD in ICP increased group was significantly higher than that in normal ICP group: (5.77 ± 0.3) mm vs. (5.01 ± 0.1) mm, with statistical difference ( P<0.05), and there was a positive correlation between ONSD and ICP. There was no significant difference in ONSD between normal ICP group and control group ( P>0.05). Conclusions:Ultrasound monitoring ONSD can reflect the level of ICP and evaluate the effect of osmotic therapy and the prognosis of patients. Bedside ultrasound examination of optic nerve sheath diameter could be used to judge ICP and to evaluate the curative effect of osmotic therapy, with high clinical application value.

Redefinition to bilayer osmotic pump tablets as subterranean river system within mini-earth via three-dimensional structure mechanism

Defining and visualizing the three-dimensional (3D) structures of pharmaceuticals provides a new and important tool to elucidate the phenomenal behavior and underlying mechanisms of drug delivery systems. The mechanism of drug release from complex structured dosage forms, such as bilayer osmotic pump tablets, has not been investigated widely for most solid 3D structures. In this study, bilayer osmotic pump tablets undergoing dissolution, as well as after dissolution in a desiccated solid state were examined, and visualized by synchrotron radiation micro-computed tomography (SR-μCT). In situ formed 3D structures at different in vitro drug release states were characterized comprehensively. A distinct movement pattern of NaCl crystals from the push layer to the drug layer was observed, beneath the semi-permeable coating in the desiccated tablet samples. The 3D structures at different dissolution time revealed that the pushing upsurge in the bilayer osmotic pump tablet was directed via peripheral "roadways". Typically, different regions of the osmotic front, infiltration region, and dormant region were classified in the push layer during the dissolution of drug from tablet samples. According to the observed 3D microstructures, a "subterranean river model" for the drug release mechanism has been defined to explain the drug release mechanism.

Study on pharmacokinetics of osmotic pump tablets of hydrochloride venlafaxine in Chinese healthy volunteers / 中国药理学通报

Aim To evaluate the pharmacokinetics and bioequivalence of two osmotic pump tablets of hydrochloride venlafaxine in Chinese healthy volunteers.Methods The fed test each enrolled twenty-six Chinese healthy volunteers in a randomized-sequence, open-label, two-period crossover single-dose oral test and reference preparations of hydrochloride venlafaxine extended-release tablets.The plasma concentrations of venlafaxine and its active metabolites O-desmethylvenlafaxine were determined by a validated liquid chromatography-tandem mass spectrometry(LC-MS/MS)method, and the pharmacokinetic parameters and bioequivalence of the two tablets were analyzed using PhoenixTM WinNonlin 6.4 software.Results The pharmacokinetic parameters of venlafaxine after single dose for the test and reference tablets were as follows: Cmax(58.50±19.47)vs(60.14±22.18)μg•L-1, AUC0-t(1 074.1±526.7)vs(1 057.9±539.7)μg•h•L-1, AUC0-∞(1 084.7±536.8)vs(1 067.8±554.0)μ g•h•L-1.The pharmacokinetic parameters of O-desmethylvenlafaxine were as follows: Cmax(101.63±29.64)vs(101.45±31.62)μg•L-1, AUC0-t(2 694.0±834.5)vs(2 702.9±946.4)μg• h•L-1, AUC0-∞(2 753.9±885.5)vs(2 753.2±988.4)μg•h•L-1.The 90% confidence intervals of the geometric mean ratios of Cmax, AUC0-t, AUC0-∞ for the test preparation and the reference preparationwere all within the equivalent interval of 80.00%-125.00%.Conclusion The test and reference preparations of hydrochloride venlafaxine extended-release tablets are bioequivalent in Chinese healthy volunteers under fed conditions.

Optimization of Diltiazem hydrochloride osmotic formulation using QBD approach

Abstract Diltiazem hydrochloride (DLH) is a calcium channel blocker useful for the treatment of angina pectoris, arrhythmia, and hypertension. DLH having a short half-life needs frequent administration for successful treatment but this poses a problem of poor patient compliance. These requirements are served by elementary osmotic pump tablets (EOP) based controlled-release (CR) systems. Quality by design (QbD) approach assists in screening various factors with subsequent assessment of critical parameters that can have a major impact on the scalability of EOP. Tablets were formulated using wet granulation method followed by osmotic coating. Factorial design based QbD strategy aided in defining the risk assessment of influential variables such as hydrophilic polymers and osmotic coat component on the in-vitro release kinetics of the designed EOP tablets. These formulated EOP systems followed zero-order kinetics, a characteristic feature of EOPs. EOP tablets were formulated applying a systematic QbD statistical approach. The formulated DLH EOP systems with improved concentration-independent behavior helped to address the challenges of IR formulation. Application of QbD strategy in ascertaining the scalability of DLH EOP formulation would help pharmaceutical industries in the translation of EOP based drug delivery systems from R&D to market.

Consumption of osmo-dehydrated Andean Berry (Vaccinium meridionale Swartz) decreases levels of pro-inflammatory biomarkers of overweight and obese adults / Consumo de agraz osmodeshidratado (Vaccinium meridionale Swartz) disminuye los niveles de biomarcadores proinflamatorios de adultos con sobrepeso y obesidad

Background: A Body Mass Index (BMI) greater than 24.9 Kg/m2 promotes chronic inflammation due to increased secretion of pro-inflammatory adipokines. Consuming fruits rich in bioactive compounds such as berries is a promising strategy to counteract this effect. Objectives: Determine the effect of osmo-dehydrated Andean Berry consumption on inflammatory biomarkers (TNF-α, IL- 6, IL-1ß, and adiponectin) and plasma antioxidant capacity in overweight and obese adults after 21 days. Methods: Andean Berry was osmo-dehydrated in 70% sucrose syrup. Antioxidant activity, proximal composition, phenolic content, microbiological analysis, and sensory analysis of the product were determined. Twenty-five obese and overweight subjects consumed 35g of osmo-dehydrated berry for 21 days. Inflammatory biomarkers and antioxidant capacity in plasma were evaluated at the beginning and end of the study. Results: Osmo-dehydrated Andean Berry presented a total phenolic content of 692.7 ± 47.4 mg Gallic Acid Equivalents/100 g. All biomarkers evaluated in the subjects showed statistically significant differences (p> 0.05), except for CRP, before and after the study. IL-6 presented the more significant reduction among all pro-inflammatory adipokines with an effect size of 18.4 Conclusions: Regular consumption of osmo-dehydrated Andean Berry contributes to decreasing pro-inflammatory biomarkers and improves the plasma antioxidant capacity of overweight and obese adults

Antecedentes: un índice de masa corporal (IMC) superior a 24.9 kg/m2 promueve la inflamación crónica debido al aumento en la secreción de adipocinas proinflamatorias. El consumo de frutas ricas en compuestos bioactivos como las bayas es una estrategia prometedora para contrarrestar este efecto. Objetivo: Determinar el efecto del consumo de agraz osmodeshidratado en biomarcadores inflamatorios (TNF-α, IL- 6, IL-1ß y adiponectina) y capacidad antioxidante plasmática de adultos con sobrepeso y obesidad después de 21 días. Métodos: El agraz fue osmo-deshidratado en jarabe de sacarosa al 70%. Se determinó la actividad antioxidante, composición proximal, contenido fenólico, análisis microbiológico y análisis sensorial del producto. Veinticinco sujetos obesos y con sobrepeso consumieron 35 g de agraz osmodeshidratado durante 21 días. Se evaluaron biomarcadores inflamatorios y capacidad antioxidante en plasma al inicio y al final del estudio. Resultados: El agraz osmodeshidratado presentó un contenido fenólico total de 692.7 ± 47.4 mg GAE / 100 g. Todos los biomarcadores evaluados en los sujetos mostraron diferencias estadísticamente significativas (p> 0.05), a excepción de la PCR, antes y después del estudio. La IL-6 presentó la mayor reducción entre todas las adipocinas proinflamatorias con un tamaño del efecto de 18.4 Conclusiones: El consumo regular de agraz osmodeshidratado contribuye a disminuir los biomarcadores proinflamatorios y mejora la capacidad antioxidante plasmática de adultos con sobrepeso y obesidad

Preparation and in vitro release of ivabradine hydrochloride elementary osmotic pump tablets / 中国药科大学学报

@#In this study, ivabradine hydrochloride (IVB) was prepared as elementary osmotic pump tablets whose administration frequency was reduced to once daily. The dissolution method was developed, and effects on drug release profiles were evaluated by single factor analysis involving suspending agents, osmotic active agents and aging process. Orthogonal test was carried out at 3 levels on 3 factors including the amount of polyoxyethylene (PEO) in the core, polyethylene glycol (PEG) percentage and weight increase of controlled-release film coatings. The final formulation consisted of IVB (16.25 mg), PEO N80 (60 mg), hypromellose E5 (10 mg), lactose (111.75 mg), magnesium stearate (2 mg); and the film coatings consisted of PEG (15%), cellulose acetate (85%), with a weight increase of 7.5%. In vitro drug release behaviors were investigated. Prepared tablets exhibited similar release profiles in different pH dissolution media, with no risk of dose dumping in 40% ethanol solutions. The osmotic pressure differences inside and outside the membrane drove drug release. IVB osmotic pump tablets could reduce the frequency of administration and improve patients'' compliance, thus with better application values.

Stability of refrigerated whole blood samples for osmotic fragility test

ABSTRACT Background: The osmotic fragility test (OFT), conventionally used for assisting the diagnosis of many erythrocyte disorders, is a manual and time-consuming analysis not daily performed in many medical laboratories. This study was aimed at defining the stability of whole blood samples used for assessing erythrocyte osmotic resistance. Methods: Twenty-one consecutive routine whole blood samples collected into 5.4 mg K2EDTA were tested immediately after collection (day 0) and at different time intervals afterward (day 1, 2, 3, 4, 7, 10 and 14) after storage at 4 °C. The OFT was performed with the Osmored Monotest (1.3% glycerol; Eurospital, Trieste, Italy). Results at the different time points were compared with those obtained at day 0 and with the reference change value (i.e., 33%). Results: The median value of both hyperosmolar and hyposmolar resistance increased from baseline, reaching statistical significance at day 7 for hyperosmolar resistance and at day 1 for hyposmolar resistance, respectively. The median relative increase of hemolysis percentage values become greater than the reference change value at day 3 for hyposmolar resistance, while this limit was never overcome for hyperosmolar resistance. A significant inverse association was found between the mean increase in hyperosmolar resistance and the baseline value of hyperosmolar resistance (r = −0.92), mean corpuscular volume (MCV; r = −0.46) or mean corpuscular hemoglobin (MCH; r = −0.44), as well as between the mean increase in hyposmolar resistance and the baseline value of hyposmolar resistance (r = −0.86), or patient age (r = −0.56). Conclusions: The sample stability seems critical for the OFT. Whole blood specimens should not be stored refrigerated at 4 °C for >2 days before testing.

Formulation and stability studies of metformin hydrochloride in a controlled porosity osmotic pump system

This study was designed to formulate, for the first time, metformin hydrochloride (MH, 850 mg/tablet) as a controlledporosity osmotic pump (CPOP) system to achieve zero-order release pattern. MH core tablet was coated with celluloseacetate membrane containing PEG 400. The effect of different percentages and molecular weights of polyethyleneoxide (PEO, 900K and 4M) in tablet core was studied. The United States Pharmacopeia (USP) apparatus II andphosphate buffer pH 6.8 were used for the release studies; meanwhile, a promising formula was tested in biorelevantmedia. The stability of some selected formulations was carried out for 6 months, at bench and accelerated conditions.Evaluation included: MH content, Differential scanning calorimetry (DSC), Scanning electron microscopy (SEM),drug release, and kinetics. Results revealed that increasing PEO percentage within the core decreased MH release.SEM verified formation of pores in the membrane that accounts for MH release. Almost all stored tablets werestable for all studied parameters. MH endothermic peak maintained its position and energy of enthalpy on storageas confirmed by DSC. MH release rate from a promising formula, following zero-order release model, increased by28% in biorelevant media compared to phosphate buffer. Subsequently, in vitro release in biorelevant media could beemployed as a tool to anticipate in vivo tone of CPOP formulations

Experience with NESTROFT for screening for thalassemia trait/ minor: evaluation against CBC and HPLC in a high prevalence region in Saurashtra, Gujarat, India

Background: Hemoglobinopathies pose a significant health burden in India. Prevention programmes can significantly reduce this burden. Although sophisticated methods of screening for β thalassemia trait are available, a cheap and simple method is beneficial for population screening. Although the Naked Eye Single Tube Red Cell Osmotic Fragility Test (NESTROFT) has been evaluated in many studies, sample sizes were small in some and many earlier studies have not done complete blood count (CBC) and High-Performance Liquid Chromatography (HPLC) in all the cases. We evaluate the suitability of NESTROFT for detection of β-thalassemia trait in a high prevalence region in Saurashtra, Gujarat.Methods: Here, 1000 unrelated individuals were studied. NESTROFT, CBC and estimation of HbA2 and HbF or other hemoglobin variants were done by HPLC.Results: Prevalence of β thalassemia trait was 7.8% in this population. NESTROFT showed an overall sensitivity and specificity of 94.87 and 85.38 respectively for the detection of β thalassaemia trait. Using red cell indices (MCH <27 pg and MCV <80 fl), One β thalassemia trait with normal indices would have been missed. Among twelve individuals with other hemoglobinopathies (HbS, HbD, HbE, δβ thalassemia trait or HPFH), seven had a positive NESTROFT while three had normal MCV & MCH values.Conclusions: NESTROFT is a cost-effective sensitive test which does not require any equipment and can be done in remote areas. It remains a useful first line screening test when large populations have to be screened.