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Biomedical subjects

Ning He

Publications and source records attributed to Ning He.

At least 19 recordsLinked to original sources

Compressed oxygen in drug stability experiments.

A drug stability experiment accelerated by compressed oxygen was established. The stability of 10% ascorbic acid solution as a model was studied and the kinetic parameters were obtained with the newly established experimental method. Because ascorbic acid degrades under both anaerobic and aerobic conditions, the total rate constant k(total) can be expressed as: k(total)=k(anaerobic) + k(aerobic), where k(anaerobic) and k(aerobic) are the rate constants of anaerobic and aerobic degradations, respectively. The k(anaerobic) can be expressed as k(anaerobic) = A(anaerobic) x exp(-E(a,anaerobic)/RT) according to Arrhenius equation, and the k(aerobic) was found to be k(aerobic) = A(aerobic) x exp(-E(a,aerobic)/RT) x p(O2) in our study.

Ascorbic Acid↗

Determination of phenytoin sodium injection and tablets by highly accurate nephelometric titration.

A highly accurate nephelometric titration method was developed for the quantitative analysis of phenytoin sodium injection and tablets. The titration operating conditions and the validation of the method were studied. Five batches of phenytoin sodium injection and tablets were determined by the proposed method and the control experiment methods, respectively. The results of the titration are comparable to those of control experiments. The proposed method is accurate and reproducible, which is considered suitable for the quantitative analysis of a large number of samples.

Anticonvulsants↗

Application of highly accurate nephelometric titration in the assaying of phenytoin sodium.

AIM: To determine phenytoin sodium by a highly accurate nephelometric titration. METHODS: The titration operating conditions were optimized and the solubility product constant of phenytoin silver precipitation was determined. RESULTS: The result of the titration is comparable to those of control experiments. CONCLUSION: The proposed method has been found to be accurate, precise, specific, reproducible, and linear.

Nephelometry and Turbidimetry↗

Determination of promethazine hydrochloride and its preparations by highly accurate nephelometric titration.

A highly accurate nephelometric titration for the determination of promethazine hydrochloride and its preparations was presented. The titration operating conditions were studied and the solubility product constant of promethazine tetraphenylboron precipitation was determined. The result of the titration is comparable to those of control experiments. The proposed method has been found to be accurate, precise, specific and linear.

Nephelometry and Turbidimetry↗

Model analysis of flux enhancement across hairless mouse skin induced by chemical permeation enhancers.

Previous permeant partitioning studies with hairless mouse skin (HMS) in the presence of several chemical skin permeation enhancers have revealed that, when such enhancers induce significant skin permeability coefficient enhancement, it is accompanied by significant enhancement in the equilibrium uptake (partitioning) of the permeant into the intercellular lipid component of the stratum corneum (SC). Particularly, it was found that the 1-alkyl-2-pyrrolidones and the 1-alkyl-2-azacycloheptanones, at aqueous solution concentrations that gave skin permeation enhancement (E) of 10 for corticosterone (CS, the permeant), enhanced the equilibrium uptake of beta-estradiol (E2beta, a surrogate permeant) from the aqueous phase into the intercellular lipids of HMS SC by a factor of 5-7. This finding raised the question of whether this uptake enhancement induced by the permeation enhancer under equilibrium conditions would be essentially the same as that determined kinetically from time-dependent permeation experiments utilizing appropriate SC membrane models and Fick's laws of diffusion to treat the data. HMS transport experiments were conducted with CS as the permeant and 1-octyl-2-pyrrolidone (OP) and 1-hexyl-2-azacyloheptanone (HAZ) as the enhancers. In treating the experimental data, a one-layer skin transport model (SC only) and a two-layer model (SC layer and the epidermis/dermis layer) were both investigated. Both the partition coefficient enhancement (E(K)) and the diffusion coefficient enhancement (E(D)) were deduced from the data treatment. The results showed that when the total transport enhancement of CS was around 11, E(K) was in the range of 6-8 and E(D) was in the range of 1.5-1.9 using both the one-layer and the two-layer models. This E(K) value was found to be in good agreement with the E2beta partition enhancement obtained directly under equilibrium conditions in previous studies. This indicates that (a) the rate-limiting domain for the transport of the lipophilic permeants across HMS and the HMS SC intercellular lipid domain probed in the equilibrium partitioning experiments are essentially the same, and (b) the total flux enhancement (E) of lipophilic permeants across HMS was driven mainly by enhancing the partitioning of the permeant into the rate-limiting domain (E(K)) and secondarily by enhancing the diffusion coefficients (E(D)) of the permeant in the domain. Comparison of the one-layer and two-layer skin model results revealed that non-steady-state transport of lipophilic compounds across HMS was better described by the two-layer model because the dermis/viable epidermis played a significant role in lipophilic permeant binding.

Algorithms↗

Functional analysis of a novel GATA3 mutation in a family with the hypoparathyroidism, deafness, and renal dysplasia syndrome.

The hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is an autosomal dominant disorder caused by mutations of a member of the GATA-binding family of transcription factors, GATA3. This dual zinc finger transcription factor binds DNA with its C-terminal zinc finger (ZnF2) and stabilizes this binding with its N-terminal zinc finger (ZnF1). ZnF1 also interacts with other zinc finger proteins, notably Friend of GATA (FOG). The HDR syndrome has been described in patients with mutations affecting both ZnF1 and ZnF2 domains; the former result in inefficient interaction with FOG, and the latter result in disruption of DNA binding. We report a patient with renal failure, hypoparathyroidism, and bilateral hearing loss. Assessment of family members indicated that the disease arose as a de novo mutation in her mother. Analysis of GATA3 in the family revealed a heterozygous missense mutation resulting in a nonconservative change of a single amino acid (R276P) in the ZnF1 domain. Functional analysis using dissociation electrophoretic mobility shift and yeast two-hybrid assays showed reduced binding affinity to the GATA motifs but normal interaction with FOG in vitro. These results are consistent with the predicted functions of human GATA3-ZnF1 from three-dimensional molecular modeling and with HDR being a result of GATA3 haploinsufficiency.

Adolescent↗

Progressive loss of renal function is an age-dependent heritable trait in type 1 autosomal dominant polycystic kidney disease.

Significant intrafamilial phenotypic variability is well documented in autosomal dominant polycystic kidney disease (ADPKD) and suggests a modifier effect. In this study, variance components analysis was performed to estimate the contribution of genetic factors for within-family renal disease variability in 406 patients from 66 type 1 ADPKD families. Overall, 39% of the study patients had ESRD at their last follow-up, and their renal survival did not differ by gender (P = 0.35, log-rank test). Because their frequency plot of creatinine clearance (Ccr) assumed a bimodal distribution with a marked kurtosis that was not improved by transformations, the study cohort was decomposed into two separate groups (non-ESRD [n = 247] and ESRD [n = 159]) in which the Ccr plots were normally distributed. The heritability (h(2)) of Ccr and age at ESRD (age(ESRD)) and the genetic correlations between these measures and their covariates were estimated. In patients without ESRD, a significant heritability was found for Ccr (h(2) = 0.42; P = 0.0015) after adjusting for age (P = 0.0001), systolic BP (P = 0.0006), and treatment with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (P = 0.00001). Birth year, gender, BMI, diastolic and mean BP, and pack-years of cigarette smoking did not significantly influence the heritability of this trait. In patients with ESRD, age(ESRD) provides a better measure than Ccr, which was very narrowly distributed. A significant heritability was found for age(ESRD) (h(2) = 0.78; P = 0.00009) in these latter patients. None of the above covariates influenced the heritability of this trait. It is concluded that a significant modifier gene effect influences the progression of renal disease in type 1 ADPKD.

Adult↗

Determination of norfloxacin by highly accurate nephelometric titration.

A highly accurate nephelometric titration for the determination of norfloxacin is presented. The titration operating conditions were studied and the solubility product constant of norfloxacin-tetraphenylboron precipitation was determined. The result of the titration is comparable to those of control experiments. The proposed method has been found to be accurate, precise, specific, and linear.

Nephelometry and Turbidimetry↗

Programmed humidifying in drug stability experiments.

The stability of penicillin potassium, as a solid state model, was investigated by a programmed humidity and temperature controlled method. An optimization calculational approach to data handling is suggested. The stability of drugs which are unstable to both heat and moisture could be studied by a single pair of experiments, one with programmed humidity control and one non-isothermal, rather than many standard isothermal studies, each at constant relative humidity. The controlling system, based on a pocket computer, was found to be accurate and reliable. The results indicated that the kinetic parameters obtained were comparable to those from isothermal studies.

Drug Stability↗

[Kinetic study on the degradation of penicillin potassium at different temperature and relative humidity].

OBJECTIVE: To perform a kinetic analysis and formulation of the degradation of penicillin potassium in the solid phase at different temperature and relative humidity. METHODS: Penicillin potassium was incubated in a temperature-and-humidity-controlled oven at different temperature and relative humidity, and was determined by HPLC at suitable time intervals during the incubation. RESULTS: The reaction rate was expressed as -dc/dt=k(c0-c+B), where c is the residual concentration, k degradation rate constant, c0 original concentration and B a constant related to original concentration of degradant. Degradation curves were fitted with c=c0-Bexp (kt)+B. The k was expressed as k=Aexp(-Ea/RT)exp(mHr), where active energy E. is 77.26 kJ/mol and constant m 0.1159. CONCLUSION: The degradation of penicillin potassium could be expressed with c=c0-Bexp [Aexp (-Ea/RT)exp (mHr)t]+B.

Drug Stability↗

[Effect of losartan on expression of Janus kinase 2 and signal transducer and activator of transcription 3 in glomeruli of diabetic rats].

OBJECTIVE: To investigate the effects of losartan on Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 in glomeruli of diabetic rats. METHODS: Sixty Wistar male rats were randomly divided into control group (n=20), diabetes group (n=20), and losartan treatment group (n=20). Diabetes was induced by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg). Losartan (10 mg/kg) was administered daily by gavage from the day following the induction of diabetes. The animals were sacrificed in the weeks 2 and 4 after STZ injection. The renal cortical tissues were obtained and glomeruli were isolated. The protein expressions of JAK2, STAT3 and tyrosine phosphorylated STAT3 (p-STAT3) were assessed respectively by Western blot. Immunoprecipitation and Western blot analysis were used to determine tyrosine phosphorylated JAK2 (p-JAK2). JAK2 and STAT3 mRNA were assayed by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Compared with the control group rats, the respective expression of JAK2, p-JAK2, STAT3, p-STAT3, JAK2 mRNA and STAT3 mRNA was significantly increased in the diabetic glomeruli without losartan treatment (all P<0.01). After treatment with losartan, the expression of p-JAK2 and p-STAT3 in the diabetic glomeruli was down-regulated (all P<0.05). However losartan had no effect on the expression of JAK2, STAT3, JAK2 mRNA and STAT3 mRNA in the diabetic glomeruli. CONCLUSION: JAK2 and STAT3 signal proteins may be involved in the kidney damage associated with diabetes. Regulation of phosphorylation of JAK2 and STAT3 may be responsible for the renal protective effects of losartan in diabetic rats.

Angiotensin II Type 1 Receptor Blockers↗

[Tubular epithelial-myofibroblast transdifferentiation and expressions of hepatocyte growth factor and Smad7 in renal tissues of rat with experimental diabetes].

OBJECTIVE: To investigate the relationship of tubular epithelial-myofibroblast transdifferentiation and the expressions of hepatocyte growth factor (HGF) and Smad7, and to elucidate the role of HGF and Smad7 in diabetic nephropathy. METHODS: Diabetes was induced in male Wistar rats with right nephrectomy and streptozotocin (STZ) administration. The expressions of cytokeratin 18 (CK18), alpha-smooth muscle actin (alpha-SMA), HGF and Smad7 were assayed with immunohistochemistry. The expressions of alpha-SMA, HGF were assayed with flow cytometry. The expression of Smad7 was assessed by Western blot. RESULTS: Compared with those in kidneys of the control group, diabetic kidneys showed down-regulated expression of CK18 and up-regulated expression of alpha-SMA. The expressions of HGF and Smad7 were increased significantly in the kidneys of diabetic rats at first, then they decreased gradually, but were still higher than those of control. CONCLUSION: The tubular epithelial cells may undergo phenotypic alterations and change to myofibroblasts. The absence of up-regulation of HGF and Smad7 may be related with the transdifferentiation of tubular cells in this animal model.

Actins↗

[The role of EPR-1 in proliferation and apoptosis in nasopharyngeal carcinoma].

OBJECTIVE: To investigate the relationship between the expression of effector cell protease receptor-1 (EPR-1) of coagulation serine protease factor Xa, proliferative index (Pi) ki-67 and apoptotic index (AI) in nasopharyngeal carcinoma. METHOD: Using immunohistochemical S-P staining and terminal deoxynucleotidyl transferase mediate dUTP nick and labeling (TUNEL) technique, the expression of EPR-1, ki-67 and AI was detected in the paraffin-embedded specimens including 42 nasopharyngeal carcinoma tissues, 42 normal nasopharyngeal tissues adjacent to the tumors tissues and 30 chronic nasopharyngitis tissues. RESULT: The positive rate of EPR-1 expression in the NPC tissues, normal nasopharyngeal tissues adjacent to the tumors and chronic nasopharyngeal tissues was 76.1%, 90.5%,100.0%, respectively. EPR-1 was positively correlated with AI and negatively with ki-67. CONCLUSION: EPR-1 play a role in increase the apoptosis and decrease the proliferation of cell. These suggest that EPR-1 may be a potential therapy for NPC.

Adolescent↗

Mechanistic studies of branched-chain alkanols as skin permeation enhancers.

As part of a long-term effort to understand the structure/function relationship between chemical permeation enhancers and skin permeation enhancement, the present study examined the influence of hydrocarbon chain branching on the effectiveness of skin permeation enhancers of the type that possesses a polar group (e.g., the hydroxyl group) attached to a hydrocarbon chain(s). The effects of x-hexanol, x-heptanol, x-octanol, and x-nonanol (where x is the position of the hydroxyl group ranging from 1 up to 5) on the transport of a probe permeant, corticosterone, across hairless mouse skin (HMS) were investigated. Isoenhancement concentrations are defined as the aqueous concentrations for which different enhancers induce the same extent of permeant transport enhancement, E, across the lipoidal pathway of stratum corneum (SC). The isoenhancement concentrations of 2-alkanol, 3-alkanol, 4-alkanol, and 5-alkanol to induce E = 10 were approximately 1.9-, 2.6-, 3.1-, and 3.9-fold higher, respectively, than those of the 1-alkanols of the same molecular formula. This suggested that the branched-chain alkanols have lower enhancer potency than the 1-alkanols of the same molecular formula; the potency decreases as the hydroxyl group moves from the end of the chain towards the center of the enhancer alkyl chain. To further investigate the mechanism(s) of action of the branched-chain alkanols as skin permeation enhancers, the equilibrium uptake of the enhancers into the hairless mouse skin stratum corneum (HMS SC) from aqueous enhancer solutions of E = 10 was determined. The data from these experiments provided a direct measure of the "intrinsic" potency of the enhancer. In the same experiments, the equilibrium partitioning (distribution) of a surrogate permeant, estradiol (E2beta), into the HMS SC was also determined and compared to the partitioning from PBS (no enhancer present). The uptake amounts (micromole/mg SC) for 1-alkanols into the intercellular lipids of the SC were found to be essentially the same at their isoenhancement concentrations. However, at their isoenhancement concentrations, the uptake amounts of the branched-chain alkanols into the intercellular lipids of HMS SC were higher than those of the 1-alkanols. These results support the view that: (1) the intrinsic potencies of the 1-alkanols are essentially the same and independent of their 1-alkyl chain length at their isoenhancement concentrations, (2) the intrinsic potencies of the branched-chain alkanols are lower than those of the normal alkanols, and (3) branching of the alkyl chain reduces the ability of the enhancer to effect lipid fluidization in the SC lipid lamellae at the target site(s). The enhancement effects of the branched-chain alkanols and the 1-alkanols at their isoenhancement concentrations upon E2beta partitioning into the SC intercellular lipids were found to be approximately the same and in the range of five- to eight-fold enhancement. The constancy of this enhancement for E2beta partitioning suggests that the mechanism of enhancement action for the branched-chain alkanols and the 1-alkanols are the same. Additionally, a good correlation of the intercellular lipid/PBS partition coefficients of both the branched-chain alkanols and the 1-alkanols with the n-octanol/PBS partition coefficients was found. This supports the view that the chemical microenvironment of the polar head group and the alkyl group of the studied enhancers at the site of skin permeation enhancer action in the SC lipid lamellae can be represented by water-saturated n-octanol for both the branched-chain alkanols and the 1-alkanols.

Alkanes↗

Mechanistic study of chemical skin permeation enhancers with different polar and lipophilic functional groups.

In a previous study, the enhancement effects on the transport of a steroidal permeant along the hairless mouse skin (HMS) stratum corneum (SC) lipoidal pathway were investigated for two homologous series of chemical enhancers: the 1-alkyl-2-pyrrolidones and the 1-alkyl-2-azacycloheptanones. The objective of the present study was to extend this investigation to a broader range of enhancers in order that generalizations with regard to the mechanistic aspects of enhancer function might be established. Specific questions to be addressed included: (a) what is the nature of the microenvironment of the enhancer site of action? (b) what is the extent of the equilibrium uptake of the enhancer from its E = 10 aqueous enhancer solution (the aqueous concentration for which the enhancer induces a tenfold transport enhancement) into the HMS SC intercellular lipid "phase"? and (c) are the microenvironment of the enhancer site of action and that for the equilibrium enhancer uptake at E = 10 relatively independent of the molecular characteristics of the enhancers (as suggested by the earlier study)? Enhancers selected for this study included: a wide range of polar head group size and polarity; n-alkyl group chain lengths from C(4) to C(12); and enhancers in which a double bond is substituted for a single bond in the hydrocarbon chain (3-alkenols) from C(5) to C(9). In addition to the main study, an ancillary set of experiments were to be conducted on the partitioning of a surrogate permeant (estradiol) into the intercellular lipid "phase" under E = 10 isoenhancement conditions to assess the extent to which the permeant partition coefficient may contribute to the permeation enhancement. The following were the principal findings of this research. First, there was very good correlation between the E = 10 isoenhancement aqueous enhancer concentrations and K(octanol/water) for all the studied enhancers. Second, the partitioning of the enhancer from the E = 10 aqueous enhancer solution into the HMS SC intercellular lipid "phase" was found to be relatively independent of the molecular characteristics for all studied enhancers, and the partition coefficients also correlated well with K(octanol/water). These results may have the following meanings: both the microenvironment of the enhancer site of action and the SC intercellular lipid "phase" involved in the enhancer partitioning experiments are well mimicked by liquid n-octanol, and the "intrinsic" potencies (as assessed by the equilibrium enhancer concentration in the microenvironment at the site of action) of the enhancers are relatively independent of the molecular characteristics of the studied enhancers. Finally, the estradiol partitioning experiments suggest the permeant partitioning into the HMS SC intercellular lipid "phase" is enhanced around five- to seven-fold when permeation is enhanced ten-fold for most of the studied enhancers; therefore, the enhancement of the permeant partition coefficient rather than the permeant diffusion coefficient seems to be more important in permeation enhancement of the SC barrier lipoidal pathway.

Animals↗

Production of a novel polygalacturonic acid bioflocculant REA-11 by Corynebacterium glutamicum.

The production of a novel polygalacturonic acid bioflocculant REA-11 from a newly isolated strain, Corynebacterium glutamicum CCTCC M201005, was investigated. Sucrose was chosen as a carbon source for REA-11 production. Complex nitrogen sources containing urea and an organic nitrogen compound enhanced both bacterial growth and REA-11 production, among which urea plus corn steep liquor was shown to be the most efficient combination. A cost-effective medium for REA-11 production mainly comprised 17 g/l sucrose, 0.45 g/l urea, and 5 ml/l corn steep liquor, under which conditions the flocculating activity reached 390 U/ml. The molar ratio of carbon to nitrogen (C/N) significantly affected REA-11 production, where a C/N ratio of 20:1 was shown to be the best. Interestingly, by simultaneously feeding sucrose and urea at a C/N ratio of 20:1 at 24 h of fermentation, REA-11 production (458 U/ml) was enhanced by 17% compared to the control. In a 10 l jar fermentor, lower dissolved oxygen tension was favorable for REA-11 production: a flocculating activity of 520 U/ml was achieved at a kappaLa of 100 h(-1). REA-11 raw product is relatively thermo-stable at acidic pH ranges of 3.0-6.5. Preliminary application studies showed that REA-11 had stronger flocculating activity to Kaolin clay suspension compared to chemical flocculants. In addition, the capability of decolorizing molasses wastewater indicates the industrial potential of this novel bioflocculant.

Carbon↗

[Influence of illuminance on the photo-reaction rate order of nitrofurazone solution].

OBJECTIVE: To explore the relationship between the illuminance and the observed order of reaction of photodegradation of nitrofurazone solution. METHODS: Studying the observed order of reaction of photodegradation of nitrofurazone solution exposed to light with three illuminance values at three concentration values respectively. RESULTS: The observed order of reaction of photodegradation increased with the decrease of concentration when the illuminance kept constant and, on the other hand, the observed order increased with the increase of illuminance when the concentration kept constant. CONCLUSION: The observed order of reaction of photodegradation of nitrofurazone solution depends on both the concentration of the drug and the illuminance of the incident light.

Drug Stability↗